Homogeneous asymmetric hydrogenation catalyst

ABSTRACT

Provide that a useful catalyst for homogeneous hydrogenation, particularly a catalyst for homogeneous asymmetric hydrogenation for hydrogenation, particularly asymmetric hydrogenation, which is obtainable with comparative ease and is excellent in economically and workability, and a process for producing a hydrogenated compound of an unsaturated compound, particularly an optically active compound using said catalyst with a high yield and optical purity.

This application is a U.S. national stage of International ApplicationNo. PCT/JP2006/313510 filed July 6, 2006.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a novel catalyst useful as homogeneoushydrogenation, in particular as homogeneous asymmetric hydrogenationand, in detail, a process for producing a hydrogenated compound of anunsaturated compound, in particularly, an optically active compoundusing said catalyst.

2. Related Art

Recently, synthesis methods using copper as a catalyst have been widelystudied in the field of asymmetric synthesis.

For example, WO01/19761 describes the asymmetric hydrosilylation ofα,β-unsaturated ester. The method described in WO01/19761, however, hassuch problems that a silyl ether form of the above-mentionedα,β-unsaturated ester need to form and is necessary for an acid oralkali treatment to obtain the objective compound, therefore the methodbecomes to complicate operation, and result in high costs because asilane waste is produced in an equivalent or more amount theoretically,further a silane compound as a reducing agent used in hydrosilylation ishighly expensive as compared with hydrogen gas.

U.S. Pat. No. 3,732,329 describes the hydrogenation of olefins by usinga complex obtained by reacting copper(I) chloride with a phosphoruscompound. In this U.S. Pat. No. 3,732,329, however, the phosphoruscompound allowed to react with copper(I) chloride is not a chiralcompound and the resulting complex is not a chiral complex, and there isno description of a reaction of a chiral ligand with a copper compound.Accordingly, the hydrogenation of the olefins described in this U.S.Pat. No. 3,732,329 is not an asymmetric hydrogenation.

React. Kinet. Catal. Lett., Vol. 9, No. 1, 73 (1978). describes theasymmetric hydrogenation of ethyl acetoacetate and acetylacetone byusing a complex obtained from Raney copper and an optically active aminoacid. However, the asymmetric hydrogenation described in this literatureis a heterogeneous system. Accordingly, the literature has such problemsthat the reaction solution does not become homogeneous and the methoddescribed in this literature becomes inferior workability because Raneycopper is required careful handling etc. In the reaction described inthis literature, the catalyst activity and the asymmetric yield in thereaction system are extremely low and do not reach a practical level.

JP-A-54-39052 and J. Org. Chem., 45, 2995 (1980). describe that arhodium complex is obtained by reacting a specific bisphosphine ligandwith a copper salt to produce achiral copper complex once, and then theresulting copper complex is reacted with a rhodium complex to carry outcopper-rhodium metal exchange reaction. They also describe an asymmetrichydrogenation using the resulting rhodium complex in a homogeneoussystem. However, in the method described in JP-A-54-39052, there is nodescription of an asymmetric hydrogenation using the copper complex as acatalyst, and the copper complex is used for only isolation andformation of the phosphine ligand. The catalyst species described inJP-A-54-39052 and J. Org. Chem., 45, 2995 (1980) are rhodium/phosphinecomplexes obtained by the metal exchange reaction. They have suchproblems that the methods described therein must be synthesized thecopper complex first, therefore said methods become to complicateoperation, in addition because rhodium is very expensive, the methodsare poor economical efficiency.

Inst. Org. Khim. im. Zelinskogo, Moscow, USSR. Kinetika Kataliz., 16(4),1081 (1975). described an asymmetric hydrogenation using a Raneycopper-ruthenium alloy and optically active tartaric acid in aheterogeneous system, and an asymmetric hydrogenation using Raney copperand optically active tartaric acid in a heterogeneous system. However,the literature has such problems that because the method described inthis literature is a heterogeneous asymmetric hydrogenation, thereaction solution does not become homogeneous, and Raney copper isrequired careful handling, therefore becomes inferior workability,further because Ruthenium is used in addition to copper, the method iscostly.

Thus there is no practical and economical asymmetric hydrogenation in ahomogeneous system using a copper complex having a chiral ligand andusing copper as the only transition metal participating in theasymmetric hydrogenation.

SUMMARY OF THE INVENTION Problem to be Resolved by the Invention

The present invention was made in view of the circumstances mentionedabove. An object of the present invention is to provide a usefulcatalyst for homogeneous hydrogenation, particularly a catalyst forhomogeneous asymmetric hydrogenation for hydrogenation, particularlyasymmetric hydrogenation, which is obtainable with comparative ease andis excellent in economically and workability. Another object of thepresent invention is to provide a process for producing a hydrogenatedcompound of an unsaturated compound, particularly an optically activecompound using said catalyst with a high yield.

The present inventors have conducted extensive research to solve theabove-mentioned problem. As a result, it has been found that a desiredhydrogenated compound of an unsaturated compound, particularly anoptically active compound thereof can be obtained by hydrogenation,particularly asymmetric hydrogenation of an unsaturated compound in ahomogeneous system using a chiral ligand and copper as a catalyst with agood yield, high economically and workability, and the present inventionwas completed.

That is, the present invention provides the following (1) to (18):

-   (1) A catalyst for homogeneous hydrogenation, which comprises a    chiral copper complex having a chiral ligand.-   (2) The catalyst for homogeneous hydrogenation according to the    above-mentioned (1), wherein the chiral copper complex is a copper    complex obtained by reacting a chiral ligand with a copper compound.-   (3) A catalyst for homogeneous hydrogenation, which comprises a    mixture of a chiral ligand and a copper compound.-   (4) The catalyst for homogeneous hydrogenation according to any one    of the above-mentioned (1) to (3), wherein the chiral ligand is at    least one member selected from the group consisting of a monodentate    ligand, a bidentate ligand, a tridentate ligand and a tetradentate    ligand.-   (5) The catalyst for homogeneous hydrogenation according to any one    of the above-mentioned (1) to (4), further comprising an additive.-   (6) The catalyst for homogeneous hydrogenation according to any one    of the above-mentioned (3) to (5), which comprises a copper    compound, a phosphorus compound represented by the formula (41):    PR¹⁵¹ ₃  (41)    wherein three R¹⁵¹s are the same or different and represent a    hydrogen atom, an optionally substituted hydrocarbon group, an    optionally substituted heterocyclic group, an optionally substituted    alkoxy group, an optionally substituted aryloxy group, an optionally    substituted aralkyloxy group, an amino group or a substituted amino    group; and an optically active diphosphine compound.-   (7) The catalyst for homogeneous hydrogenation according to any one    of the above-mentioned (3) to (5), which comprises a copper complex    represented by the formula (51):    [CuL³(PR²⁰¹ ₃)_(n31)]_(n32)  (51)    wherein L³ represents a ligand, three R²⁰¹s are the same or    different and represent a hydrogen atom, an optionally substituted    hydrocarbon group, an optionally substituted heterocyclic group, an    optionally substituted alkoxy group, an optionally substituted    aryloxy group, an optionally substituted aralkyloxy group, an amino    group or a substituted amino group; and n31 and n32 independently    represent a natural number; and an optically active diphosphine    compound.-   (8) The catalyst according to any one of the above-mentioned (1) to    (7), wherein the catalyst for homogeneous hydrogenation is a    catalyst for homogeneous asymmetric hydrogenation.-   (9) A process for producing a hydrogenated compound of an    unsaturated compound, which comprises subjecting an unsaturated    compound to a homogeneous hydrogenation in the presence of the    catalyst for homogeneous hydrogenation according to any one of the    above-mentioned (1) to (8).-   (10) The process according to the above-mentioned (9), wherein the    unsaturated compound is a prochiral compound, the catalyst for    homogeneous hydrogenation is a catalyst for homogeneous asymmetric    hydrogenation, and the obtained hydrogenated compound of the    unsaturated compound is an optically active compound.-   (11) A homogeneous hydrogenation method comprising using the    catalyst for homogeneous hydrogenation according to any one of the    above-mentioned (1) to (7).-   (12) A homogeneous asymmetric hydrogenation method comprising using    the catalyst for homogeneous asymmetric hydrogenation according to    the above-mentioned (8).    (13) A chiral copper complex represented by the formula (61):    [L¹¹L¹²CuL¹³]_(n35)  (61)    wherein L¹¹ represents a bidentate optically active phosphorus    compound; L¹² represents a phosphorus compound different from L¹¹;    L¹³ represents a ligand; and n35 represents a natural number.-   (14) A catalyst for homogeneous hydrogenation, which comprises the    chiral copper complex according to the above-mentioned (13).-   (15) The catalyst according to the above-mentioned (14), wherein the    catalyst for homogeneous hydrogenation is a catalyst for homogeneous    asymmetric hydrogenation.-   (16) A process for producing an optically active compound, which    comprises subjecting a prochiral compound to a homogeneous    asymmetric hydrogenation in the presence of the catalyst for    homogeneous asymmetric hydrogenation according to the    above-mentioned (15).-   (17) A homogeneous hydrogenation method comprising using the    catalyst for homogeneous hydrogenation according to the    above-mentioned (14).-   (18) A homogeneous asymmetric hydrogenation method comprising using    the catalyst for homogeneous asymmetric hydrogenation according to    the above-mentioned (15).

The present invention is to provide a novel catalyst for homogeneoushydrogenation, in particularly, a novel catalyst for homogeneousasymmetric hydrogenation, which is useful in carrying out hydrogenation,particularly asymmetric hydrogenation in the presence of hydrogen gas,and carrying out transfer hydrogenation, particular asymmetric transferhydrogenation in the coexistence with a hydrogen donor. Variousunsaturated compounds are carrying out by hydrogenation, particularlyasymmetric hydrogenation in the presence of the catalyst in a homogenoussystem to give hydrogenated compounds of said unsaturated compounds,particularly optically active compounds thereof, which are useful asintermediates of medicines and agrochemicals, perfumes and the like,efficiently with a good optical purity, in addition improvingworkability and economical efficiency. Thus, the present invention getsgood results in the above-mentioned effect.

DETAILED DESCRIPTION OF THE INVENTION

In the present invention, the term “ligand” means an atom and atomicgroup forming a complex with copper (Cu), in addition to an atom andatomic group capable of forming the complex with copper (Cu).

[1] Catalyst for Homogeneous Hydrogenation

The catalyst for homogeneous hydrogenation of the present inventioncontains achiral copper complex having a chiral ligand. In addition, thecatalyst for homogeneous hydrogenation of the present invention containsa mixture of a chiral ligand and a copper compound.

Here, in the present invention, the term “homogeneous” means a state inwhich a catalyst for homogeneous hydrogenation having catalytic activityis substantially dissolved on the occasion of hydrogenation, and a statein which said catalyst is dissolved and can be dissolved in thesolution. The state in which the catalyst is dissolved in a solution isthat the catalyst for homogeneous hydrogenation is dissolved at thestart of the hydrogenation. Also, the state in which the catalyst can bedissolved in a solution is that the catalyst for homogeneoushydrogenation can be dissolved at the start of the hydrogenation. Thestate, for example, includes that the used catalyst for homogeneoushydrogenation is dissolved by a rise in reaction temperature or aprogress of the reaction, and a reaction condition such as a kind of theused unsaturated compound or a solvent and reaction temperature. Thestate further includes that, in the case that a boundary surface existsin the reaction system, the property of the reaction system hardlychange in the boundary surface, and the state is homogeneous or almosthomogeneous through the whole reaction. As described above, the term“homogeneous” used in the present invention is a state in which thechiral copper complex or the copper compound used as the catalyst forhomogenous hydrogenation is substantially dissolved on the occasion ofhydrogenation, and a state that a substrate (unsaturated compound) usedin the homogeneous hydrogenation, an additive used as necessary, or theinactivated the catalyst for homogeneous hydrogenation may exist as asolid in the reaction system.

In the present invention, further, the hydrogenation using the catalystfor homogeneous hydrogenation is a hydrogenation in which only copper isinvolved as a transition metal. That is, the catalyst for homogeneoushydrogenation of the present invention is a catalyst in which atransition metal other than copper is not substantially contained, andcopper is used as a sole transition metal.

[1-1] Chiral Copper Complex

The chiral copper complex used in the catalyst for homogeneoushydrogenation of the present invention is, as described above, a chiralcopper complex having a chiral ligand and is capable of using any chiralcopper complex having a chiral ligand, and it is preferable for a chiralcopper complex obtained by reacting a chiral ligand with a coppercompound to use. Here, “the chiral copper complex obtained by reacting”includes a chiral copper complex which is reacted a chiral ligand and acopper compound, i) followed by post-treatment and the like as necessaryto give, ii) followed by post-treatment and the like and then isolationand/or purification to give, iii) without post-treatment, isolation,purification or the like to give, that is used a reaction mixture as itstands, and the like.

The chiral copper complex having a chiral ligand used in the presentinvention (Hereinafter may be referred to simply as “a chiral coppercomplex”) may be chiral copper complex having a chiral ligand asdescribed above, and includes, for example, a chiral copper complexdescribed in Handbook of Enantioselective Catalysis (VCH, 1993); J. Am.Chem. Soc. 2001, 123, 5843; J. Org. Chem., 1998, 63, 6090; Angew. Chem.Int., Ed. 2004, 43, 1679; Dalton. Trans. 2003, 1881; Organic Letters,Vol. 6, No. 14, 2305 (2004); and the like, and a chiral copper complexcapable of using in an asymmetric synthesis and the like. Theabove-mentioned chiral copper complex used in the present invention isparticularly preferably a chiral copper complex obtained by reacting achiral ligand with a copper complex.

1) Chiral Ligand

The chiral ligand used in the present invention may be any ligand whichhas an optically active site, is an optically active compound, andusable as a chiral ligand. The above-mentioned chiral ligand includes,for example, chiral ligands described in Catalytic Asymmetric Synthesis(Wiley-VCH, 2000); Handbook of Enantioselective Catalysis withTransition Metal Complex (VCH, 1993); ASYMMETRIC CATALYSIS IN ORGANICSYNTHESIS (John Wiley & Sons Inc. (1994)); WO 2005/070875; and the like.

In more detail, the chiral ligand used in the present inventionincludes, for example, a monodentate ligand, a bidentate ligand, atridentate ligand, a tetradentate ligand, and the like.

The monodentate ligand includes, for example, an optically activephosphorus compound, an optically active amine compound, an opticallyactive alcohol compound, an optically active sulfur compound anoptically active carbene compound and the like.

The optically active phosphorus compound may be a phosphorus compoundhaving an optically active site in its molecule to form an opticallyactive compound, and includes, for example, an optically activephosphorus compound represented by the following formulae (6) to (8).These optically active phosphorus compounds represented by the formulae(6) to (8) are an optically active phosphorus compound having anoptically active site in its molecule.PR¹ ₃  (6)wherein three of R¹ are the same or different and represents anoptionally substituted hydrocarbon group, an optionally substitutedheterocyclic group, an optionally substituted alkoxy group, anoptionally substituted aryloxy group, an optionally substitutedaralkyloxy group, an amino group or a substituted amino group; and twoor three in three of R¹ may be combined with each other to form a ring.

wherein R² represents an optionally substituted hydrocarbon group or asubstituted amino group; Q¹ represents a spacer; Z¹ and Z² independentlyrepresent an oxygen atom, a sulfur atom or —NR⁴— (wherein R⁴ representsa hydrogen atom or a protecting group).

wherein R³ represents a hydrogen atom or an optionally substitutedhydrocarbon group; Q² represents a spacer; Z³ and Z⁴ independentlyrepresent an oxygen atom, a sulfur atom or —NR⁵— (wherein R⁵ representsa hydrogen atom or a protecting group).

The respective groups used in the formulae (6) to (8) are explained indetail.

The optionally substituted hydrocarbon group represented by R¹ to R³includes a hydrocarbon group and a substituted hydrocarbon group.

The hydrocarbon group includes, for example, an alkyl group, an alkenylgroup, an alkynyl group, an alkadienyl group, an aryl group, an aralkylgroup and the like.

The alkyl group may be linear, branched or cyclic and includes, forexample, an alkyl group having 1 to 20, preferably 1 to 15, morepreferably 1 to 10 carbon atom(s). Specific examples of the alkyl groupinclude, for example, methyl, ethyl, n-propyl, 2-propyl, n-butyl,1-methylpropyl, isobutyl, tert-butyl, n-pentyl, 1-methylbutyl,tert-pentyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, n-hexyl,1-methylpentyl, 1-ethylbutyl, 2-methylpentyl, 3-methylpentyl,4-methylpentyl, 2-methylpentan-3-yl, heptyl, octyl, nonyl, decyl,lauryl, stearyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl andthe like.

The alkenyl group may be linear or branched and includes, for example,an alkenyl group having 2 to 20, preferably 2 to 15, more preferably 2to 10 carbon atoms. Specific examples of the alkenyl group include, forexample, vinyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl,nonenyl, decenyl and the like.

The alkynyl group may be linear or branched and includes, for example,an alkynyl group having 2 to 20, preferably 2 to 15, more preferably 2to 10 carbon atoms. Specific examples of the alkynyl group include, forexample, ethynyl, propynyl, butynyl, pentynyl, hexynyl and the like.

The alkadienyl group may be linear, branched or cyclic and includes, forexample, an alkadienyl group having two double bonds in arbitrarypositions in the chain of the above-mentioned alkyl group and having 4or more, preferably 4 to 20, more preferably 4 to 15, further preferably4 to 10 carbon atoms. Specific examples of the alkadienyl group include,for example, 1,3-butadienyl, 2,3-dimethyl-1,3-butadienyl and the like.

The aryl group includes, for example, an aryl group having 6 to 20,preferably 6 to 15 carbon atoms. Specific examples of the aryl groupinclude, for example, phenyl, naphthyl, anthryl, biphenyl and the like.

The aralkyl group includes, for example, an aralkyl group having 7 to20, preferably 7 to 15 carbon atoms and an aralkyl group wherein atleast one hydrogen atom of the above-mentioned alkyl group issubstituted with the above-mentioned aryl group. Specific examples ofthe aralkyl group include, for example, benzyl, 1-phenylethyl,2-phenylethyl, 1-phenylpropyl, 3-naphthylpropyl and the like.

The substituted hydrocarbon group (a hydrocarbon group having asubstituent) includes a hydrocarbon group wherein at least one hydrogenatom of the above-mentioned hydrocarbon group is substituted with asubstituent, and examples thereof include, for example, a substitutedalkyl group, a substituted alkenyl group, a substituted alkynyl group, asubstituted alkadienyl group, a substituted aryl group, a substitutedaralkyl group and the like. The substituent will be described later (Thesame applies hereinafter).

Specific examples of the substituted alkyl group include, for example,methoxymethyl, ethoxymethyl and the like.

Specific examples of the substituted aryl group include, for example,tolyl (for example, 4-methylphenyl), xylyl (for example,3,5-dimethylphenyl), 4-methoxy-3,5-dimethylphenyl,4-methoxy-3,5-di-tert-butylphenyl and the like.

The optionally substituted heterocyclic group represented by R¹ includesa heterocyclic group and a substituted heterocyclic group. Theheterocyclic group includes an aliphatic heterocyclic group and anaromatic heterocyclic group.

The aliphatic heterocyclic group includes, for example, an aliphaticheterocyclic group having 2 to 14 carbon atoms and a 3- to 8-membered,preferably 5- to 6-membered monocyclic, polycyclic or fused ringaliphatic heterocyclic group containing at least 1, preferably 1 to 3heteroatom(s) such as a nitrogen atom, an oxygen atom and/or a sulfuratom. Specific examples of the aliphatic heterocyclic group include, forexample, pyrrolidyl-2-one, piperidino, piperazinyl, morpholino,morpholinyl, tetrahydrofuryl, tetrahydropyranyl, thiolanyl and the like.

The aromatic heterocyclic group includes, for example, an aromaticheterocyclic group having 2 to 15 carbon atoms and a 3- to 8-membered,preferably 5- to 6-membered monocyclic, polycyclic or fused ringaromatic heterocyclic group containing at least 1, preferably 1 to 3heteroatom(s) such as a nitrogen atom, an oxygen atom and/or a sulfuratom. Specific examples of the aromatic heterocyclic group include, forexample, furyl, thienyl, pyridyl, pyrimidyl, pyrazyl, pyridazyl,pyrazolyl, imidazolyl, oxazolyl, thiazolyl, benzofuryl, benzothienyl,quinolyl, isoquinolyl, quinoxalyl, phthalazyl, quinazolyl, naphthyridyl,cinnolyl, benzoimidazolyl, benzoxazolyl, benzothiazolyl, acridyl,acrydinyl and the like.

The substituted heterocyclic group (a heterocyclic group having asubstituent) includes a heterocyclic group wherein at least one hydrogenatom of the above-mentioned heterocyclic group is substituted with thesubstituent, and examples thereof include a substituted aliphaticheterocyclic group and a substituted aromatic heterocyclic group.

The optionally substituted alkoxy group includes an alkoxy group and asubstituted alkoxy group.

The alkoxy group may be linear, branched or cyclic and includes, forexample, an alkoxy group having 1 to 20 carbon atom(s). Specificexamples of the alkoxy group include, for example, methoxy, ethoxy,n-propoxy, 2-propoxy, n-butoxy, 2-butoxy, isobutoxy, tert-butoxy,n-pentyloxy, 2-methylbutoxy, 3-methylbutoxy, 2,2-dimethylpropyloxy,n-hexyloxy, 2-methylpentyloxy, 3-methylpentyloxy, 4-methylpentyloxy,heptyloxy, octyloxy, nonyloxy, decyloxy, cyclohexyloxy and the like. Theabove-mentioned alkoxy group is particularly preferably an alkoxy grouphaving 1 to 10, more preferably 1 to 6 carbon atom(s).

The substituted alkoxy group (an alkoxy group having a substituent)includes an alkoxy group in which at least one hydrogen atom of theabove-mentioned alkoxy group is substituted with the substituent.

The optionally substituted aryloxy group includes an aryloxy group and asubstituted aryloxy group.

The aryloxy group includes, for example, an aryloxy group having 6 to 20carbon atoms. Specific examples of the aryloxy group include, forexample, phenyloxy, naphthyloxy, anthryloxy and the like. Theabove-mentioned aryloxy group is particularly preferably an aryloxygroup having 6 to 14 carbon atoms.

The substituted aryloxy group (an aryloxy group having a substituent)includes an aryloxy group in which at least one hydrogen atom of theabove-mentioned aryloxy group is substituted with the substituent.

The optionally substituted aralkyloxy group includes an aralkyloxy groupand a substituted aralkyloxy group.

The aralkyloxy group includes, for example, an aralkyloxy group having 7to 20 carbon atoms. Specific examples of the aralkyloxy group include,for example, benzyloxy, 2-phenylethoxy, 1-phenylpropoxy,2-phenylpropoxy, 3-phenylpropoxy, 1-phenylbutoxy, 2-phenylbutoxy,3-phenylbutoxy, 4-phenylbutoxy, 1-phenylpentyloxy, 2-phenylpentyloxy,3-phenylpentyloxy, 4-phenylpentyloxy, 5-phenylpentyloxy,1-phenylhexyloxy, 2-phenylhexyloxy, 3-phenylhexyloxy, 4-phenylhexyloxy,5-phenylhexyloxy, 6-phenylhexyloxy and the like. The above-mentionedaralkyloxy group is particularly preferably an aralkyloxy group having 7to 12 carbon atoms.

The substituted aralkyloxy group (an aralkyloxy group having asubstituent) includes an aralkyloxy group wherein at least one hydrogenatom of the above-mentioned aralkyloxy group is substituted with thesubstituent.

The substituted amino group represented by R¹ and R² includes a linearor cyclic amino group wherein one or two hydrogen atom(s) is/aresubstituted with a substituent (s) such as an amino-protecting group andthe like. The above-mentioned amino-protecting group may be any groupsthat are usually used as an amino-protecting group, and include, forexample, groups described as an amino-protecting group in “PROTECTIVEGROUPS IN ORGANIC SYNTHESIS THIRD EDITION (JOHN WILEY & SONS INC.(1999))”. Specific examples of the amino-protecting group include, forexample, an optionally substituted hydrocarbon group (for example, analkyl group, an aryl group, an aralkyl group and the like), anoptionally substituted acyl group, an optionally substitutedalkoxycarbonyl group, an optionally substituted aryloxycarbonyl group,an optionally substituted aralkyloxycarbonyl group, a substitutedsulfonyl group and the like.

The optionally substituted hydrocarbon group as exemplified by specificexamples of the amino-protecting group, such as, for example, the alkylgroup, the aryl group, the aralkyl group and the like, may have the samemeaning as the respective groups of the optionally substitutedhydrocarbon group described above.

Specific examples of the amino group substituted with the alkyl group,that is, an alkyl-substituted amino group include, for example, a mono-or dialkylamino group such as N-methylamino, N,N-dimethylamino,N,N-diethylamino, N,N-diisopropylamino, N-cyclohexylamino and the like.

Specific examples of the amino group substituted with the aryl group,that is, an aryl-substituted amino group include, for example, a mono-or diarylamino group such as N-phenylamino, N,N-diphenylamino,N-naphthylamino, N-naphthyl-N-phenylamino and the like.

Specific examples of the amino group substituted with the aralkyl group,that is, an aralkyl-substituted amino group include, for example, amono- or diaralkylamino group such as N-benzylamino, N,N-dibenzylaminoand the like. Also, examples thereof include a di-substituted aminogroup such as N-methyl-N-phenylamino, N-benzyl-N-methylamino and thelike.

The optionally substituted acyl group includes an acyl group and asubstituted acyl group.

The acyl group may be linear, branched or cyclic and includes, forexample, an acyl group having 1 to 20 carbon atom(s) derived from anacid such as carboxylic acid, sulfonic acid, sulfinic acid, phosphinicacid, phosphonic acid and the like.

The acyl group derived from carboxylic acid includes an acyl groupderived from carboxylic acid such as aliphatic carboxylic acid andaromatic carboxylic acid, and includes, for example, an acyl grouprepresented by the formula: —COR^(b); wherein R^(b) represents ahydrogen atom, an optionally substituted hydrocarbon group or anoptionally substituted heterocyclic group (Said optionally substitutedhydrocarbon group and said optionally substituted heterocyclic group maybe the same respective groups as described above). Specific examples ofthe acyl group derived from carboxylic acid include, for example,formyl, acetyl, propionyl, butyryl, pivaloyl, pentanoyl, hexanoyl,lauroyl, stearoyl, benzoyl, 1-naphthoyl, 2-naphthoyl and the like. Theabove-mentioned acyl group is particularly preferably an acyl grouphaving 2 to 18 carbon atoms.

The sulfonic acid-derived acyl group includes a sulfonyl group. Thesulfonyl group includes a substituted sulfonyl group and includes, forexample, a substituted sulfonyl group represented by the formula:R^(c)—SO₂—; wherein R^(c) represents an optionally substitutedhydrocarbon group, an optionally substituted heterocyclic group, anamino group, a substituted amino group, an optionally substituted alkoxygroup, an optionally substituted aryloxy group or an optionallysubstituted aralkyloxy group (Said optionally substituted hydrocarbongroup, said optionally substituted heterocyclic group, the substitutedamino group, the optionally substituted alkoxy group, the optionallysubstituted aryloxy group and the optionally substituted aralkyloxygroup may be the same respective groups as described above). Specificexamples of the sulfonyl group include, for example, methanesulfonyl,trifluoromethanesulfonyl, benzenesulfonyl, p-toluenesulfonyl and thelike. The sulfonyl group wherein R^(c) is the amino group or thesubstituted amino group is an aminosulfonyl group. Specific examples ofthe aminosulfonyl group include, for example, aminosulfonyl,dimethylaminosulfonyl, diethylaminosulfonyl, diphenylaminosulfonyl andthe like. The substituted sulfonyl group wherein R^(c) is the optionallysubstituted alkoxy group, the optionally substituted aryloxy group orthe optionally substituted aralkyloxy group is an alkoxxysulfonyl group.Specific examples of the alkoxysulfonyl group include, for example,methoxysulfonyl, ethoxysulfonyl, phenoxysulfonyl, benzyloxysulfonyl andthe like.

The sulfinic acid-derived acyl group includes a sulfinyl group. Thesulfinyl group includes a substituted sulfinyl group, and includes, forexample, a substituted sulfinyl group represented by the formula:R^(d)—SO—; wherein R^(d) represents an optionally substitutedhydrocarbon group, a optionally substituted heterocyclic group or asubstituted amino group (Said optionally substituted hydrocarbon group,said optionally substituted heterocyclic group and said substitutedamino group may be the same respective groups as described above).Specific examples of the sulfinyl group include, for example,methanesulfinyl, tert-butylsulfinyl, benzenesulfinyl and the like.

The phosphinic acid-derived acyl group includes a phosphinyl group. Thephosphinyl group includes a substituted phosphinyl group, and includes,for example, a substituted sulphinyl group represented by the formula:(R^(e))₂—PO—; wherein two of R^(e) may be the same or different andrepresent an optionally substituted hydrocarbon group (Said optionallysubstituted hydrocarbon group may be the same optionally substitutedhydrocarbon group as described above). Specific examples of thephosphinyl group include, for example, dimethylphosphinyl,diphenylphosphinyl and the like.

The phosphonic acid-derived acyl group includes a phosphonyl group. Thephosphonyl group includes a substituted phosphonyl group, and includes,for example, a substituted phosphonyl group represented by the formula:(R^(f)O)₂—PO—; wherein two of R^(f) may be the same or different andrepresent an optionally substituted hydrocarbon group (Said theoptionally substituted hydrocarbon group may be the same optionallysubstituted hydrocarbon group as described above). Specific examples ofthe phosphonyl group include, for example, dimethylphosphonyl,diphenylphosphonyl and the like.

The substituted acyl group (an acyl group having a substituent) includesan acyl group where in at least one hydrogen atom of the above-mentionedacyl group is substituted with the substituent.

Specific examples of the amino group substituted with the optionallysubstituted acyl group, that is, an acylamino group includes, forexample, formylamino, acetylamino, propionylamino, pivaloylamino,pentanoylamino, hexanoylamino, benzoylamino and the like.

Specific examples of the amino group substituted with the sulfonyl groupamong the acyl group, that is, a sulfonylamino group include, forexample, —NHSO₂CH₃, —NHSO₂C₆H₅, —NHSO₂C₆H₄—CH₃, —NHSO₂CF₃, —NHSO₂OCH₃,—NHSO₂NH₂ and the like.

Specific examples of the amino group substituted with the optionallysubstituted alkoxy group, the optionally substituted aryloxy group orthe optionally substituted aralkyloxy group among the acyl group, thatis, an alkoxysulfonylamino group include, for example,methoxysulfonylamino, ethoxysulfonylamino, phenoxysulfonylamino,benzyloxysulfonylamino and the like.

The optionally substituted alkoxycarbonyl group includes analkoxycarbonyl group and a substituted alkoxycarbonyl group.

The alkoxycarbonyl group may be linear, branched or cyclic and includes,for example, an alkoxycarbonyl group having 2 to 20 carbon atoms.Specific examples of the alkoxycarbonyl group include, for example,methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, 2-propoxycarbonyl,n-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl,hexyloxycarbonyl, 2-ethylhexyloxycarbonyl, lauryloxycarbonyl,stearyloxycarbonyl, cyclohexyloxycarbonyl and the like.

The substituted alkoxycarbonyl group (an alkoxycarbonyl group having asubstituent) includes an alkoxycarbonyl group wherein at least onehydrogen atom of the above-mentioned alkoxycarbonyl group is substitutedwith the substituent.

Specific examples of the amino group substituted with the optionallysubstituted alkoxycarbonyl group, that is, an alkoxycarbonylamino groupincludes, for example, methoxycarbonylamino, ethoxycarbonylamino,n-propoxycarbonylamino, n-butoxycarbonylamino, tert-butoxycarbonylamino,pentyloxycarbonylamino, hexyloxycarbonylamino and the like.

The optionally substituted aryloxycarbonyl group includes anaryloxycarbonyl group and a substituted aryloxycarbonyl group.

The aryloxycarbonyl group includes, for example, an aryloxycarbonylgroup having 7 to 20 carbon atoms. Specific examples of thearyloxycarbonyl group include, for example, phenoxycarbonyl,naphthyloxycarbonyl and the like.

The substituted aryloxycarbonyl group (an aryloxycarbonyl group having asubstituent) includes an aryloxycarbonyl group wherein at least onehydrogen atom of the above-mentioned aryloxycarbonyl group issubstituted with the substituent.

Specific examples of the amino group substituted with the optionallysubstituted aryloxycarbonyl group, that is, an aryloxycarbonylaminogroup includes, for example, an amino group wherein one hydrogen atom ofan amino group is substituted with the above-mentioned aryloxycarbonylgroup, and specific examples thereof include, for example,phenoxycarbonylamino, naphthyloxycarbonylamino and the like.

The optionally substituted aralkyloxycarbonyl group includes anaralkyloxycarbonyl group and a substituted aralkyloxycarbonyl group.

The aralkyloxycarbonyl group includes, for example, an aralkyloxycarbonyl group having 8 to 20-carbon atoms. Specific examples of thearalkyloxycarbonyl group include, for example, benzyloxycarbonyl,phenethyloxycarbonyl, 9-fluorenylmethyloxycarbonyl and the like.

The substituted aralkyloxycarbonyl group (an aralkyloxycarbonyl grouphaving a substituent) includes an aralkyloxycarbonyl group wherein atleast one hydrogen atom of the above-mentioned aralkyloxycarbonyl groupis substituted with the substituent.

Specific examples of the amino group substituted with the optionallysubstituted aralkyloxycarbonyl group, that is, anaralkyloxycarbonylamino group includes, for example,benzyloxycarbonylamino, phenethyloxycarbonylamino,9-fluorenylmethyloxycarbonylamino and the like.

Also, the cyclic amino group includes, for example, an amino group inwhich a nitrogen-containing ring is formed by bonding through analkylene group. Said alkylene group may be linear or branched andincludes, for example, an alkylene group having 1 to 6 carbon atom(s).Specific examples of the alkylene group include, for example, methylene,ethylene, propylene, trimethylene, 2-methylpropylene,2,2-dimethylpropylene, 2-ethylpropylene and the like. Theabove-mentioned alkylene group may have an oxygen atom, a nitrogen atom,a carbonyl group and the like, or a double bond in an arbitrary positionof at the terminal position or in the chain of the alkylene group.

The spacer represented by Q¹ and Q² includes an optionally substituteddivalent organic group and the like. Specific examples of the optionallysubstituted divalent organic group include, for example, an alkylenegroup, an arylene group, a heteroarylene group and the like. Also, thedivalent organic group may have at least one heteroatom or heteroatomicgroup such as an oxygen atom, a carbonyl group, a sulfur atom, an iminogroup, a substituted imino group and the like, in an arbitrary positionof the terminal position or in the chain of said organic group. Further,the spacer may have an optically active site.

The alkylene group may be linear or branched and includes, for example,an alkylene group having 1 to 10 carbon atom(s). Specific examples ofthe alkylene group include, for example, methylene, ethylene, propylene,trimethylene, tetramethylene, pentamethylene, hexamethylene,heptamethylene octamethylene, nonamethylene, decamethylene,2-methylpropylene, 2,2-dimethylpropylene, 2-ethylpropylene and the like.

The arylene group includes, for example, an arylene group having 6 to 20carbon atoms. Specific examples of the arylene group include, forexample, phenylene, biphenyldiyl, binaphthalenediyl, bisbenzodioxoldiyland the like.

The heteroarylene group includes, for example, a heteroarylene grouphaving 2 to 20 carbon atoms and a 3- to 8-membered, preferably 5- to6-membered monocyclic, polycyclic or fused ring heteroarylene groupcontaining at least 1, preferably-1 to 3 heteroatom(s) such as anitrogen atom, an oxygen atom and/or a sulfur atom. Specific examples ofthe heteroarylene group include, for example, bipyridinediyl,bisbenzothioldiyl, bisthioldiyl and the like.

The substituted imino group includes an imino group wherein the hydrogenatom of an imino group (—NH—) is substituted with an amino-protectinggroup. The amino-protecting group may be the same amino-protecting groupas described above in the substituted amino group.

The divalent organic group having a heteroatom or a heteroatomic groupincludes —CH₂—O—CH₂—, —C₆H₄—O—C₆H₄— and the like.

These divalent organic groups may be substituted with a substituentdescribed later.

When the spacer has an optically active site, specific examples of thespacer having an optically active site include, for example,1,2-dimethylethylene, 1,2-cyclohexylene, 1,2-diphenylethylene,1,2-di(4-methylphenyl)ethylene, 1,2-dicyclohexylethylene,1,3-dimethyltrimethylene, 1,3-diphenyltrimethylene,1,4-dimethyltetramethylene, 1,3-dioxolane-4,5-diyl, biphenyldiyl,binaphthalenediyl and the like. These spacer shaving an optically activesite include those in (R), (S), (R,R) or (S,S) form.

The protecting group represented by R⁴ in —NR⁴-represented by Z¹ and Z²,and the protecting group represented by R⁵ in —NR⁵— represented by Z³and Z⁴, may be the same amino-protecting group as described above in thesubstituted amino group.

The substituent includes, for example, an optionally substitutedhydrocarbon group, an optionally substituted heterocyclic group, ahalogen atom, a halogenated hydrocarbon group, an optionally substitutedalkoxy group, an optionally substituted aryloxy group, an optionallysubstituted aralkyloxy group, an optionally substituted heteroaryloxygroup, an optionally substituted alkylthio group, an optionallysubstituted arylthio group, an optionally substituted aralkylthio group,an optionally substituted heteroarylthio group, an optionallysubstituted acyl group, an optionally substituted acyloxy group, anoptionally substituted alkoxycarbonyl group, an optionally substitutedaryloxycarbonyl group, an optionally substituted aralkyloxycarbonylgroup, an optionally substituted alkylenedioxy group, a nitro group, anamino group, a substituted amino group, a cyano group, a sulfo group, asubstituted silyl group, a hydroxy group, a carboxy group, an optionallysubstituted alkoxythiocarbonyl group, an optionally substitutedaryloxythiocarbonyl group, an optionally substitutedaralkyloxythiocarbonyl group, an optionally substitutedalkylthiocarbonyl group, an optionally substituted arylthiocarbonylgroup, an optionally substituted aralkylthiocarbonyl group, anoptionally substituted carbamoyl group, a substituted phosphino group,an oxo group and the like.

As the substituent, the optionally substituted hydrocarbon group, theoptionally substituted heterocyclic group, the optionally substitutedalkoxy group, the optionally substituted aryloxy group, the optionallysubstituted aralkyloxy group, the optionally substituted acyl group, theoptionally substituted alkoxycarbonyl group, the optionally substitutedaryloxycarbonyl group, the optionally substituted aralkyloxycarbonylgroup, and the substituted amino group may be the same respective groupsas described above and the respective groups explained in thesubstituted amino group.

The halogen atom includes fluorine, chlorine, bromine, iodine and thelike.

The halogenated hydrocarbon group includes those groups wherein at leastone hydrogen atom of the above-mentioned hydrocarbon group ishalogenated (for example, fluorinated, chlorinated, brominated oriodinated). The halogenated hydrocarbon group includes, for example, ahalogenated alkyl group, a halogenated aryl group and a halogenatedaralkyl group.

The halogenated alkyl group includes, for example, a halogenated alkylgroup having 1 to 20 carbon atom(s). Specific examples thereof include,chloromethyl, bromomethyl, chloroethyl, bromopropyl, fluoromethyl,fluoroethyl, fluoropropyl, fluorobutyl, fluoropentyl, fluorohexyl,fluoroheptyl, fluorooctyl, fluorononyl, fluorodecyl, difluoromethyl,difluoroethyl, fluorocyclohexyl, trifluoromethyl, 2,2,2-trifluoroethyl,3,3,3-trifluoropropyl, pentafluoroethyl, 3,3,4,4,4-pentafluorobutyl,perfluoro-n-propyl, perfluoroisopropyl, perfluoro-n-butyl,perfluoroisobutyl, perfluoro-tert-butyl, perfluoro-sec-butyl,perfluoropentyl, perfluoroisopentyl, perfluoro-tert-pentyl,perfluoro-n-hexyl, perfluoroisohexyl, perfluoroheptyl, perfluorooctyl,perfluorononyl, perfluorodecyl, perfluorooctylethyl,perfluorocyclopropyl, perfluorocyclopentyl, perfluorocyclohexyl and thelike. The above-mentioned halogenated alkyl group is particularlypreferably a halogenated alkyl group having 1 to 10 carbon atom(s).

The halogenated aryl group includes, for example, a halogenated arylgroup having 6 to 20 carbon atoms. Specific examples thereof include2-fluorophenyl, 3-fluorophenyl, 4-fluorphenyl, 2-chlorophenyl,3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl,4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl,2-trifluoromethylphenyl, 3-trifluoromethylphenyl,4-trifluoromethylphenyl, 2-trichloromethylphenyl,3-trichloromethylphenyl, 4-trichloromethylphenyl, perfluorophenyl,perfluoronaphthyl, perfluoroanthryl, perfluorobiphenyl and the like. Theabove-mentioned halogenated aryl group is particularly preferably ahalogenated aryl group having 6 to 15 carbon atoms.

The halogenated aralkyl group includes those groups wherein at least onehydrogen atom of the above-mentioned aralkyl group is substituted withthe halogen atom, and includes, for example, a halogenated aralkyl grouphaving 7 to 20 carbon atoms. Specific examples thereof include2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-chlorobenzyl,3-chlorobenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-iodobenzyl,2-trifluoromethylbenzyl, 3-trifluoromethylbenzyl,4-trifluoromethylbenzyl, 4-trichloromethylbenzyl, perfluorobenzyl andthe like. The above-mentioned halogenated aralkyl group is particularlypreferably a having 6 to 15 carbon atoms.

The optionally substituted heteroaryloxy group includes a heteroaryloxygroup and a substituted heteroaryloxy group.

The heteroaryloxy group includes, for example, a heteroaryloxy grouphaving 2 to 20 carbon atoms, preferably C2 to C15 carbon atoms,heteroaryloxy groups each containing at least 1, preferably 1 to 3,heteroatom(s) such as a nitrogen atom, an oxygen atom and a sulfur atom.Specific examples of the heteroaryloxy group include 2-pyridyloxy,2-pyrazyloxy, 2-pyrimidyloxy, 2-quinolyloxy and the like.

The substituted heteroaryloxy group (a heteroaryloxy group having asubstituent) includes a heteroaryloxy group wherein at least onehydrogen atom of the above-mentioned aralkyloxy group is substitutedwith the substituent. The substituent may be the same substituent asdescribed above unless otherwise specified (The same applieshereinafter).

The optionally substituted alkylthio group includes an alkylthio groupand a substituted alkylthio group.

The alkylthio group may be linear, branched or cyclic and includes, forexample, an alkylthio group having 1 to 20 carbon atom(s). Specificexamples of the alkylthio group include, for example, methylthio,ethylthio, n-propylthio, 2-propylthio, n-butylthio, 2-butylthio,isobutylthio, tert-butylthio, pentylthio, hexylthio, cyclohexylthio andthe like. The above-mentioned alkylthio group is particularly preferablyan alkylthio group having 1 to 10, more preferably 1 to 6 carbonatom(s).

The substituted alkylthio group (an alkylthio group having asubstituent) includes an alkylthio group wherein at least one hydrogenatom of the above-mentioned alkylthio group is substituted with thesubstituent.

The optionally substituted arylthio group includes an arylthio group anda substituted arylthio group.

The arylthio group includes, for example, an arylthio group having 6 to20 carbon atoms. Specific examples of the arylthio group includephenylthio, naphthylthio and the like.

The above-mentioned arylthio group is particularly preferably anarylthio group having 6 to 14 carbon atoms.

The substituted arylthio group (an arylthio group having a substituent)includes an arylthio group wherein at least one hydrogen atom of theabove-mentioned arylthio group is substituted with the substituent.

The optionally substituted aralkylthio group includes an aralkylthiogroup and a substituted aralkylthio group.

The aralkylthio group includes, for example, an aralkylthio group having7 to 20 carbon atoms. Specific examples of the aralkylthio groupinclude, for example, benzylthio, 2-phenethylthio and the like. Theabove-mentioned aralkylthio group is particularly preferably anaralkylthio group having 7 to 12 carbon atoms.

The substituted aralkylthio group (an aralkylthio group having asubstituent) includes an aralkylthio group wherein at least one hydrogenatom of the above-mentioned aralkylthio group is substituted with thesubstituent.

The optionally substituted heteroarylthio group includes aheteroarylthio group and a substituted heteroarylthio group.

The heteroarylthio group includes, for example, a heteroarylthio grouphaving 2 to 20 carbon atoms, preferably 2 to 15 carbon atoms, containingat least 1, preferably 1 to 3, heteroatom(s) such as a nitrogen atom, anoxygen atom and a sulfur atom. Specific examples of the heteroarylthiogroup include, for example, 4-pyridylthio, 2-benzimidazolylthio,2-benzoxazolylthio, 2-benzothiazolylthio and the like.

The substituted heteroarylthio group (a heteroarylthio group having asubstituent) includes a heteroarylthio group wherein at least onehydrogen atom of the above-mentioned heteroarylthio group is substitutedwith the substituent.

The optionally substituted acyloxy group includes an acyloxy group and asubstituted acyloxy group.

The acyloxy group includes, for example, an acyloxy group having 2 to 20carbon atoms derived from a carboxylic acid such as an aliphaticcarboxylic acid and an aromatic carboxylic acid. Specific examples ofthe acyloxy group include, for example, acetoxy, propionyloxy,butyryloxy, pivaloyloxy, pentanoyloxy, hexanoyloxy, lauroyloxy,stearoyloxy, benzoyloxy and the like. The acyloxy group is particularlypreferably a having 2 to 18 carbon atoms acyloxy group.

The substituted acyloxy group (an acyloxy group having a substituent)includes an acyloxy group wherein at least one hydrogen atom of theabove-mentioned acyloxy group is substituted with the substituent.

The optionally substituted alkoxythiocarbonyl group includes analkoxythiocarbonyl group and a substituted alkoxythiocarbonyl group.

The alkoxythiocarbonyl group may be linear, branched or cyclic andincludes, for example, an alkoxythiocarbonyl group having 2 to 20 carbonatoms. Specific examples of the alkoxythiocarbonyl group include, forexample, methoxythiocarbonyl, ethoxythiocarbonyl, n-propoxythiocarbonyl,2-propoxythiocarbonyl, n-butoxythiocarbonyl, tert-butoxythiocarbonyl,pentyloxythiocarbonyl, hexyloxythiocarbonyl,2-ethylhexyloxythiocarbonyl, lauryloxythiocarbonyl,stearyloxythiocarbonyl, cyclohexyloxythiocarbonyl and the like.

The substituted alkoxythiocarbonyl group (an alkoxythiocarbonyl grouphaving a substituent) includes an alkoxythiocarbonyl group wherein atleast one hydrogen atom of the above-mentioned alkoxythiocarbonyl groupis substituted with the substituent.

The optionally substituted aryloxythiocarbonyl group includes anaryloxythiocarbonyl group and a substituted aryloxythiocarbonyl group.

The aryloxythiocarbonyl group includes, for example, anaryloxythiocarbonyl group having 7 to 20 carbon atoms. Specific examplesof the aryloxythiocarbonyl group include, for example,phenoxythiocarbonyl, naphthyloxythiocarbonyl and the like.

The substituted aryloxythiocarbonyl group (an aryloxythiocarbonyl grouphaving a substituent) includes an aryloxythiocarbonyl group wherein atleast one hydrogen atom of the above-mentioned aryloxythiocarbonyl groupis substituted with the substituent.

The optionally substituted aralkyloxythiocarbonyl group includes anaralkyloxythiocarbonyl group and a substituted aralkyloxythiocarbonylgroup.

The aralkyloxythiocarbonyl group includes, for example, anaralkyloxythiocarbonyl group having 8 to 20 carbon atoms. Specificexamples of the aralkyloxythiocarbonyl group include, for example,benzyloxythiocarbonyl, phenethyloxythiocarbonyl,9-fluorenylmethyloxythiocarbonyl and the like.

The substituted aralkyloxythiocarbonyl group (an aralkyloxythiocarbonylgroup having a substituent) includes an aralkyloxythiocarbonyl groupwherein at least one hydrogen atom of the above-mentionedaralkyloxythiocarbonyl group is substituted with the substituent.

The optionally substituted alkylthiocarbonyl group includes analkylthiocarbonyl group and a substituted alkylthiocarbonyl group.

The alkylthiocarbonyl group may be linear, branched or cyclic andincludes, for example, an alkylthiocarbonyl group having 2 to 20 carbonatoms. Specific examples of the alkylthiocarbonyl group include, forexample, methylthiocarbonyl, ethylthiocarbonyl, n-propylthiocarbonyl,for example, 2-propylthiocarbonyl, n-butylthiocarbonyl,tert-butylthiocarbonyl, pentylthiocarbonyl, hexylthiocarbonyl,2-ethylhexythiocarbonyl, laurylthiocarbonyl, stearylthiocarbonyl,cyclohexylthiocarbonyl and the like.

The substituted alkylthiocarbonyl group (an alkylthiocarbonyl grouphaving a substituent) includes an alkylthiocarbonyl group wherein atleast one hydrogen atom of the above-mentioned alkylthiocarbonyl groupis substituted with the substituent.

The optionally substituted arylthiocarbonyl group includes anarylthiocarbonyl group and a substituted arylthiocarbonyl group.

The arylthiocarbonyl group includes, for example, an arylthiocarbonylgroup having 7 to 20 carbon atoms. Specific examples of thearylthiocarbonyl group include phenylthiocarbonyl, naphthylthiocarbonyland the like.

The substituted arylthiocarbonyl group (an arylthiocarbonyl group havinga substituent) includes an arylthiocarbonyl group wherein at least onehydrogen atom of the above-mentioned arylthiocarbonyl group issubstituted with the substituent.

The optionally substituted aralkylthiocarbonyl group includes anaralkylthiocarbonyl group and a substituted aralkylthiocarbonyl group.

The aralkylthiocarbonyl group includes, for example, anaralkylthiocarbonyl group having 8 to 20 carbon atoms. Specific examplesof the aralkylthiocarbonyl group include, for example,benzylthiocarbonyl, phenethylthiocarbonyl, 9-fluorenylmethylthiocarbonyland the like.

The substituted aralkylthiocarbonyl group (an aralkylthiocarbonyl grouphaving a substituent) includes an aralkylthiocarbonyl group wherein atleast one hydrogen atom of the above-mentioned aralkylthiocarbonyl groupis substituted with the substituent.

The optionally substituted carbamoyl group includes a carbamoyl groupand a substituted carbamoyl group.

The substituted carbamoyl group includes a carbamoyl group wherein oneor two hydrogen atom(s) of an amino group in the carbamoyl group aresubstituted with a substituent such as an optionally substitutedhydrocarbon group and the like. The optionally substituted hydrocarbongroup is the same hydrocarbon group as described above. Specificexamples of the substituted carbamoyl group include, for example,N-methylcarbamoyl, N,N-diethylcarbamoyl, N-phenylcarbamoyl and the like.

The substituted phosphino group includes a phosphino group wherein oneor two hydrogen atom(s) is substituted with a substituent such as anoptionally substituted hydrocarbon group and the like. The optionallysubstituted hydrocarbon group is the same hydrocarbon group as describedabove. Specific examples of the substituted phosphino group include, forexample, dimethylphosphino, diethylphosphino, diphenylphosphino,methylphenylphosphino and the like.

The substituted silyl group includes, for example, a tri-substitutedsilyl group wherein three hydrogen atoms in a silyl group aresubstituted with a substituent such as the above-mentioned optionallysubstituted hydrocarbon group and the above-mentioned optionallysubstituted alkoxy group. Specific examples of the substituted silylgroup include, for example, trimethylsilyl, triethylsilyl,tri(2-propyl)silyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl,triphenylsilyl, tert-butylmethoxyphenylsilyl, tert-butoxydiphenylsilyland the like.

The substituted silyloxy group includes, for example, a tri-substitutedsilyloxy group having 1 to 18 carbon atom(s) tri-substituted silyloxygroups wherein 1 to 3 hydrogen atom(s) in a silyloxy group issubstituted with a substituent such as the above-mentioned optionallysubstituted hydrocarbon group and the above-mentioned optionallysubstituted alkoxy group. Specific examples of the substituted silyloxygroup include, for example, trimethylsilyloxy, triethylsilyloxy,tri(2-propyl)silyloxy, tert-butyldimethylsilyloxy,tert-butyldiphenylsilyloxy, triphenylsilyloxy,tert-butylmethoxyphenylsilyloxy, tert-butoxydiphenylsilyloxy and thelike.

The optionally substituted alkylenedioxy group includes an alkylenedioxygroup and a substituted alkylenedioxy group.

The alkylenedioxy group includes, for example, an alkylenedioxy grouphaving 1 to 3 carbon atom(s). Specific examples of the alkylenedioxygroup include, for example, methylenedioxy, ethylenedioxy,trimethylenedioxy, propylenedioxy and the like.

The substituted alkylenedioxy group (an alkylenedioxy group having asubstituent) includes an alkylenedioxy group wherein at least onehydrogen atom of the above-mentioned alkylenedioxy group is substitutedwith the substituent. Specific examples of the substituted alkylenedioxygroup include difluoromethylenedioxy and the like.

Specific examples of the optically active phosphorus compound include,for example, optically active phosphorus compounds shown below:

The optically active amine compound may be an amine compound having anoptically active site in its molecule to form an optically activecompound.

The optically active amine compound includes an optically activealiphatic amine compound, an optically active aromatic amine compound,an optically active nitrogen-containing heterocyclic compound and thelike.

Specific examples of the optically active aliphatic amine compoundinclude, for example, optically active menthylamine, optically active1-phenylethylamine and the like. Specific examples of the opticallyactive aromatic amine compound include, for example, an aniline compoundhaving an optically active site and the like. Specific examples of theoptically active nitrogen-containing compound include, for example, thecompounds such as pyridine, piperidine, piperazine and oxazoline, havingan optically active site, and the like. Here, the optically activeoxazoline compound of the monodentate ligand is also included in theoptically active amine compound.

The optically active alcohol compound may be an alcohol compound havingan optically active site in its molecule to form an optically activecompound. Specific examples of the optically active alcohol compoundinclude, for example, the optically active alcohol compounds shownbelow:

The optically active sulfur compound may be a sulfur compound having anoptically active site in its molecule to form an optically activecompound. Specific examples of the optically active sulfur compoundinclude, for example, the optically active sulfur compound shown below:

The optically active carbene compound may be a carbene compound havingan optically active site in its molecule to form an optically activecompound. Specific examples of the optically active carbene compoundinclude, for example, the optically active carbene compounds shownbelow:

The bidentate ligand includes a bidentate optically active phosphoruscompound such as an optically active diphosphine compound, aphosphine-phosphite compound and the like, an optically active diaminecompound, an optically active aminoalcohol compound, an optically activediol compound, an optically active aminophosphine compound, an opticallyactive phosphinoalcohol compound, an optically active aminothiolcompound, an optically active bisoxazoline compound and the like.

The bidentate optically active phosphorus compound may be a bidentatephosphorus compound having an optically active site in its molecule toform an optically active compound, and includes, for example, anoptically active phosphorus compound represented by the followingformula (10). The optically active phosphorus compound represented bythe formula (10) is a phosphorus compound having an optically activesite in its molecule.R⁶R⁷P-Q³-PR⁸R⁹  (10)wherein R⁶ to R⁹ independently represent an optionally substitutedhydrocarbon group, an optionally substituted heterocyclic group, anoptionally substituted alkoxy group, an optionally substituted aryloxygroup, or an optionally substituted aralkyloxy group; and Q³ representsa spacer. Also, R⁶ and R⁷ and P and/or R⁸ and R⁹ and P or R⁶ and/or R⁷and Q³ or R⁸ and/or R⁹ and Q³ may be combined to form a ring. Providedthat, R⁶ to R⁹ and Q³ may be such a group that the phosphorus compoundrepresented by the formula (10) is capable of forming the opticallyactive phosphorus compound.

In the formula (10), the optionally substituted hydrocarbon group, theoptionally substituted heterocyclic group, the optionally substitutedalkoxy group, the optionally substituted aryloxy group and theoptionally substituted aralkyloxy group represented by R⁶ to R⁹ may bethe same respective groups as described above. The spacer represented byQ³ may also be the same as the spacer explained in the above-mentionedQ¹ and Q².

Specific examples of the above-mentioned optically active phosphoruscompound include, for example, an optically active diphosphine compound,that is an optically active form, such as1,2-bis(anisylphenylphosphino)ethane (DIPAMP),1,2-bis(alkylmethylphosphino)ethane (BisP*),2,3-bis(diphenylphosphino)butane (CHIRAPHOS),1,2-bis(diphenylphosphino)propane (PROPHOS),2,3-bis(diphenylphosphino)-5-norbornene (NORPHOS),2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane(DIOP), 1-cyclohexyl-1,2-bis(diphenylphosphino)ethane (CYCPHOS),1-substituted-3,4-bis(diphenylphosphino)pyrrolidine (DEGPHOS),2,4-bis-(diphenylphosphino)pentane (SKEWPHOS), 1,2-bis(substitutedphospholano)benzene (DuPHOS), 1,2-bis(substituted phospholano)ethane(BPE), 1-((substituted phospholano)-2-(diphenylphosphino)benzene(UCAP-Ph), 1-(bis(3,5-dimethylphenyl)phosphino)-2-(substitutedphospholano)benzene (UCAP-DM), 1-((substitutedphospholano)-2-(bis(3,5-di(tert-butyl)-4-methoxyphenyl)phosphino)benzene(UCAP-DTBM), 1-((substitutedphospholano)-2-(di-naphthalen-1-yl-phosphino)benzene (UCAP-(1-Nap)),2,2′-bis(diphenylphosphino)-1,1′-bicylopentane (BICP),2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP),2,2′-bis(diphenylphosphino)-1,1′-(5,5′,6,6′,7,7′,8,8″-octahydronaphthyl) (H₈-BINAP), 2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl(TOL-BINAP), 2,2′-bis(di(3,5-dimethylphenyl)phosphino)-1,1′-binaphthyl(DM-BINAP), 2,2′-bis(diphenylphosphino)-6,6′-dimethyl-1,1′-biphenyl(BICHEP), (4,4′-bi-1,3-benzodioxol)-5,5′-diylbis(diphenylphosphine)(SEGPHOS),(4,4′-bi-1,3-benzodioxol)-5,5′-diylbis[bis(3,5-dimethylphenyl)phosphine](DM-SEGPHOS),[(4S)-[4,4′-bi-1,3-benzodioxol]-5,5′-diyl]bis[bis[3,5-bis(1,1-dimethylethyl)-4-methoxyphenyl]phosphine](DTBM-SEGPHOS) and the like. In addition, the optically activephosphorus compound includes optically active phosphorus compounds shownbelow:

The bidentate optically active diamine compound may be a diaminecompound having an optically active site in its molecule to form anoptically active compound, and includes, for example, an opticallyactive diamine compound represented by the following formula (11). Theoptically active diamine compound represented by the following formula(11) is a diamine compound having an optically active site in itsmolecule.R¹⁰R¹¹N—C_(f)(R⁴R⁵)-Q⁴-C_(g)(R¹⁶R¹⁷)—NR¹²R¹³  (11)wherein R¹⁰ to R¹³ independently represent a hydrogen atom, anoptionally substituted hydrocarbon group, an optionally substitutedheterocyclic group, a substituted sulfonyl group or a protecting group;R¹⁴ to R¹⁷ independently represent a hydrogen atom, an optionallysubstituted hydrocarbon group or an optionally substituted heterocyclicgroup; Q⁴ represents a spacer or a direct link; and f and gindependently represent 0 or 1; provided that R¹⁴ and R¹⁵ and C_(f),and/or R¹⁶ and R¹⁷ and C_(g) may be combined to form a ring; R¹⁰ or R¹¹and R¹⁴ or R¹⁵ and C_(f) and N, and/or R¹² or R¹³ and R¹⁶ or R¹⁷ andC_(g) and N may be combined to form a ring such as a carbon ring, analiphatic ring and the like; R¹⁴ or R¹⁵ and R¹⁶ or R¹⁷ may be combinedto form a ring; R¹⁰ and R¹¹ and N, and/or R¹² and R¹³ and N may becombined to form a ring; R¹⁰ and R¹¹ and N, and/or R¹² and R¹³ and N maybe combined to form a heterocyclic ring such as a pyridine ring and thelike; and R¹⁴ or R¹⁵ and R¹⁶ or R¹⁷ and C_(f) and Q⁴ and C_(g) may becombined to form a ring such as an aromatic ring, an aliphatic ring andthe like.

In the formula (11), the respective groups represented by R¹⁰ to R¹⁷,that is, an optionally substituted hydrocarbon group, an optionallysubstituted heterocyclic group, a substituted sulfonyl group and aprotecting group may be the same respective groups as described above.The spacer represented by Q⁴ may be the same spacer as explained in theabove-mentioned Q¹, Q² and the like. The ring formed by combining R¹⁴and R¹⁵, and/or R¹⁶ and R¹⁷; R¹⁰ or R¹¹ and R¹⁴ or R¹⁵, and/or R¹² orR¹³ and R¹⁶ or R¹⁷; R¹⁴ or R¹⁵ and R¹⁶ or R¹⁷; and R¹⁰ and R¹¹, and/orR¹² and R¹³ include, for example, a ring such as a carbon ring, aheterocyclic ring and the like, formed by bonding through an alkylenegroup. The alkylene group may be the same alkylene group as explained inthe spacer of Q¹ and Q² in the formulae (7) and (8). Specific examplesof the formed ring include, for example, a carbon ring such as aliphaticrings such as a cyclohexane ring and a benzene ring; a heterocyclic ringsuch as a pyridine ring and a piperidine ring; and the like. Theseformed rings may further have substituents described above.

The optically active diamine compound includes an optically activearomatic diamine an optically active aliphatic diamine, an opticallyactive bisoxazoline compounds and the like.

The optically active bisoxazoline compound in the optically activediamine compound is a bidentate optically active bisoxazoline compound.The bidentate optically active bisoxazoline compound may be abisoxazoline compound having an optically active site in its molecule toform an optically active compound, and includes, for example, anoptically active bisoxazoline compound represented by the followingformula (17). The optically active bisoxazoline compound represented bythe following formula (17) is a bisoxazoline compound having anoptically active site in its molecule. Provided that, theabove-mentioned optically active oxazoline compound may be a tridentateor tetradentate ligand depending on a type of the spacer or thesubstituent on the oxazoline ring.

wherein the oxazoline rings A and B represent an optionally substitutedoxazoline ring; and Q¹⁰ represents a spacer or a direct link.

In the formula (17), the oxazoline ring represented by the oxazolinerings A and B includes an oxazoline ring (that is, an oxazoline ring nothaving a substituent) and a substituted oxazoline ring (that is, anoxazoline ring having a substituent). The substituent on the optionallysubstituted oxazoline ring may be the same substituent as describedabove. The spacer represented by Q¹⁰ may be the same spacer as describedabove as Q¹ and Q².

Specific examples of the optically active diamine compound include, forexample, 1,2-diphenylethylenediamine,1,2-bis(4-methoxyphenyl)ethylenediamine,1,2-dicyclohexylethylenediamine,1,2-di(4-N,N-dimethylaminophenyl)ethylenediamine,1,2-di(4-N,N-diethylaminophenyl)ethylenediamine,1,2-di(4-N,N-dipropylaminophenyl)ethylenediamine,1,2-(N-benzenesulfonyl)-1,2-di(4-N,N-dimethylaminophenyl)ethylenediamine,1,2-(N-p-toluenesulfonyl)-1,2-di(4-N,N-dimethylaminophenyl)ethylenediamine,1,2-(N-methanesulfonyl)-1,2-di(4-N,N-dimethylaminophenyl)ethylenediamine,1,2-(N-trifluoromethanesulfonyl)-1,2-di(4-N,N-dimethylaminophenyl)ethylenediamine,1,2-(N-benzenesulfonyl)-1,2-di(4-N,N-diethylaminophenyl)ethylenediamine,1,2-(N-benzenesulfonyl)-1,2-di(4-N,N-dipropylaminophenyl)ethylenediamine,1,2-di(4-sulfonylphenyl)ethylenediamine, 1,2-di(4-sodiumoxysulfonylphenyl)ethylenediamine, 1,2-cyclohexanediamine,1,2-cycloheptanediamine, 2,3-dimethylbutanediamine,1-methyl-2,2-diphenylethylenediamine,1-isobutyl-2,2-diphenylethylenediamine,1-isopropyl-2,2-diphenylethylenediamine,1-methyl-2,2-di(p-methoxyphenyl)ethylenediamine,1-isobutyl-2,2-di(p-methoxyphenyl)ethylenediamine,1-isopropyl-2,2-di(p-methoxyphenyl)ethylenediamine,1-benzyl-2,2-di(p-methoxyphenyl)ethylenediamine,1-methyl-2,2-dinaphthylethylenediamine,1-isobutyl-2,2-dinaphthylethylenediamine,1-isopropyl-2,2-dinaphthylethylenediamine,bis[N-(2,4,6-trimethylphenyl)methyl-1,2-diphenylethylenediamine,N,N′-bis(phenylmethyl)-1,2-diphenyl-1,2-ethylenediamine,N,N′-bis(mesitylmethyl)-1,2-diphenyl-1,2-ethylenediamine,N,N′-bis(naphthylmethyl)-1,2-diphenyl-1,2-ethylenediamine and the like,that are the optically active form. In addition, the optically activediamine compound includes optically active diamine compounds shownbelow:

These optically active diamine compounds include (1R,2R), (1S,2S),(1R,2S) and (1S,2R) as the optically active form, and these opticallyactive diamine compounds are particularly preferably the (1R,2R) and(1S,2S) forms (here, unless otherwise specified with respect to theoptically active form, the same applies to compounds having a similarstructure, such as an optically active aminoalcohol compound describedlater). Specific examples of the (1R,2R) and (1S,2S) form of theoptically active diamine compound include, for example,

-   (1R,2R)-1,2-diphenylethylenediamine,-   (1S,2S)-1,2-diphenylethylenediamine,-   (1R,2R)-1,2-di(4-N,N-dimethylaminophenyl)ethylenediamine,-   (1S,2S)-1,2-di(4-N,N-dimethylaminophenyl)ethylenediamine,-   (1R,2R)-1,2-di(4-N,N-diethylaminophenyl)ethylenediamine,-   (1S,2S)-1,2-di(4-N,N-diethylaminophenyl)ethylenediamine,-   (1R,2R)-1,2-di(4-N,N-dipropylaminophenyl)ethylenediamine,-   (1S,2S)-1,2-di(4-N,N-dipropylaminophenyl)ethylenediamine    and the like.

Also, specific examples of the optically active bisoxazoline compoundinclude, for example,

-   (S,S)-2,6-bis(4-isopropyl-2-oxazolin-2-yl)pyridine,-   (R,R)-2,6-bis(4-isopropyl-2-oxazolin-2-yl)pyridine,-   (S,S)-2,6-bis(4-phenyl-2-oxazolin-2-yl)pyridine,-   (R,R)-2,6-bis(4-phenyl-2-oxazolin-2-yl)pyridine,-   (S,S)-2,2′-isopropylidenebis(4-phenyl-2-oxazoline),-   (R,R)-2,2′-isopropylidenebis(4-phenyl-2-oxazoline),-   (S,S)-(−)-2,2′-isopropylidenebis(4-tert-butyl-2-oxazoline),-   2,2′-methylenebis[(4R or 4S)-phenyl-5,5-dimethyloxazoline],-   2,2′-methylenebis[(4R or 4S)-phenyl-5,5-diethyloxazoline],-   2,2′-methylenebis[(4R or-   4S)-phenyl-5,5-di-n-propyloxazoline], 2,2′-methylenebis [(4R or    4S)-phenyl-5,5-di-1-propyloxazoline],-   2,2′-methylenebis[(4R or-   4S)-phenyl-5,5-dicyclohexyloxazoline],-   2,2′-methylenebis [(4R or 4S)-phenyl-5,5-diphenyloxazoline],-   2,2′-methylenebis[(4R or    4S)-phenyl-5,5-di-(2-methylphenyl)oxazoline],-   2,2′-methylenebis[(4R or    4S)-phenyl-5,5-di-(3-methylphenyl)oxazoline],-   2,2′-methylenebis[(4R or    4S)-phenyl-5,5-di-(4-methylphenyl)oxazoline],-   2,2′-methylenebis[(4R or    4S)-phenyl-5,5-di-(2-methoxyphenyl)oxazoline],-   2,2′-methylenebis[(4R or    4S)-phenyl-5,5-di-(3-methoxyphenyl)oxazoline],-   2,2′-methylenebis[(4R or    4S)-phenyl-5,5-di-(4-methoxyphenyl)oxazoline],-   2,2′-methylenebis[spiro((4R or    4S)-phenyloxazoline-5,1′-cyclobutane)],-   2,2′-methylenebis[spiro((4R or    4S)-phenyloxazoline-5,1′-cyclopentane)],-   2,2′-methylenebis[spiro((4R or    4S)-phenyloxazoline-5,1′-cyclohexane)],-   2,2′-methylenebis[spiro((4R or    4S)-phenyloxazoline-5,1′-cycloheptane)] and the like.

The bidentate optically active aminoalcohol compound may be anaminoalcohol compound having an optically active site in its molecule toform an optically active compound, and includes, for example, anoptically active aminoalcohol compound represented by the followingformula (12). The optically active aminoalcohol compound represented bythe following formula (12) is an aminoalcohol compound having anoptically active site in its molecule.R¹⁸R¹⁹N—C_(f)(R²⁰R²¹)-Q⁵-C_(g)(R²²R²³)—OH  (12)wherein R¹⁸ and R¹⁹ independently represent a hydrogen atom, anoptionally substituted hydrocarbon group, an optionally substitutedheterocyclic group, a substituted sulfonyl group or a protecting group;R²⁰ to R²³ independently represent a hydrogen atom, an optionallysubstituted hydrocarbon group or an optionally substituted heterocyclicgroup; Q⁵ represents a spacer or a direct link; and f and g have thesame meanings as defined above; provided that R²⁰ and R²¹ and C_(f),and/or R²² and R²³ and C_(g) may be combined to form a ring; R¹⁸ or R¹⁹and R²⁰ or R² and N and C_(f) may be combined to form a ring such as acarbon ring and an aliphatic ring; R¹⁸ and R¹⁹ may be combined to form aring; R¹⁸ and R¹⁹ and N may be combined to form a heterocyclic ring suchas a pyridine ring and the like; and R²⁰ and R² and C_(f) and Q⁵ may becombined to form a ring such as an aliphatic ring and an aromatic ring.

In the formula (12), the respective groups represented by R¹⁸ to R²³,that is, an optionally substituted hydrocarbon group, an optionallysubstituted heterocyclic group, a substituted sulfonyl group and aprotecting group may be the same respective groups as described above.The spacer represented by Q⁵ may be the same spacer as explained in theabove-mentioned Q¹ and Q².

The above-mentioned optically active aminoalcohol compound includes anoptically active aromatic aminoalcohol, an optically active aliphaticaminoalcohol and the like. Specific examples of the optically activeaminoalcohol compound include, for example, the optically activealiphatic aminoalcohol such as 1-amino-2-propanol, 2-amino-1-butanol,alaminol, leucinol, isoleucinol, 2-aminocyclohexanol,4-aminocyclohexanol and 2-aminocyclohexanemethanol; the optically activearomatic aminoalcohol such as phenylglycinol, phenylalaminol, ephedrine,norephedrine, pseudoephedrine, 2-amino-1,2-diphenylethanol and2-benzylaminocyclohexane methanol; and the like. In addition, theoptically active aminoalcohol compound includes optically activeaminoalcohols shown below:

These optically active aminoalcohol compounds include (1R,2R), (1S,2S),(1R,2S) and (1S,2R) as the optically active form, and these opticallyactive aminoalcohol compounds are particularly preferably the (1R,2R)and (1S,2S) form.

The bidentate optically active diol compound may be a diol compoundhaving an optically active site in its molecule to form an opticallyactive compound, and includes, for example, optically active diolcompounds represented by the following formula (13). The opticallyactive diol compound represented by the following formula (13) is a diolcompound having an optically active site in its molecule.HO—C_(f)(R²⁴R²⁵)-Q⁶-C_(g)(R²⁶R²⁷)—OH  (13)wherein R²⁴ to R²⁷ independently represent a hydrogen atom, anoptionally substituted hydrocarbon group or an optionally substitutedheterocyclic group; Q⁶ represents a spacer or a direct link; and f and ghave the same meanings as defined above; provided that R²⁴ and R²⁵ andC_(f), and/or R²⁶ and R²⁷ and C_(g) may be combined to form a ring; andR²⁴ or R²⁵ and C_(f) and Q⁶ and C_(g) and R²⁶ or R²⁷ may be combined toform a ring such as an aliphatic ring and an aromatic ring.

In the formula (13), the optionally substituted hydrocarbon group andthe optionally substituted heterocyclic group represented by R²⁴ to R²⁷may be the same respective groups as described above. The spacerrepresented by Q⁶ may be the same spacer as described above as Q¹ andQ².

Specific examples of the optically active diol compound include, forexample, optically active diol compounds shown below:

These optically active diol compounds include (1R,2R), (1S,2S), (1R,2S)and (1S,2R) as the optically active form, and these optically activediol compounds are particularly preferably the (1R,2R) and (1S,2S) form.

The bidentate optically active aminophosphine compound may be anaminophosphine compound having an optically active site in its moleculeto form an optically active compound, and includes, for example, anoptically active aminophosphine compound represented by the followingformula (14). The optically active aminophosphine compound representedby the following formula (14) is an aminophosphine compound having anoptically active site in its molecule.R⁶R⁷P-Q⁷-C_(g)(R¹⁶R¹⁷)—NR¹²R¹³  (14)wherein Q⁷ represents a spacer or a direct link; and R⁶, R⁷, R¹², R¹³,R¹⁶ and R¹⁷ and g have the same meanings as defined above; provided thatR⁶ and R⁷ and P, R⁶ and/or R⁷ and P and Q⁷, R¹⁶ and R¹⁷ and C_(g), R¹²or R¹³ and R¹⁶ or R¹⁷ and C_(g), and/or R¹² and R¹³ and N may becombined to form a ring; R¹² and R¹³ and N may be combined to form aheterocyclic ring such as a pyridine ring and the like; and R¹⁶ or R¹⁷may be combined to form ring such as an aromatic ring and an aliphaticring.

In the formula (13), the spacer represented by Q⁷ may also be the samespacer as explained in the above-mentioned Q¹ and Q².

Specific examples of the optically active aminophosphine compoundinclude, for example, optically active compounds shown below:

The bidentate optically active phosphinoalcohol compound may be aphosphinoalcohol compound having an optically active site in itsmolecule to form an optically active compound, and includes, forexample, optically active phosphinoalcohol compounds represented by thefollowing formula (15). The optically active phosphinoalcohol compoundrepresented by the following formula (15) is a phosphinoalcohol compoundhaving an optically active site in its molecule.R⁶R⁷P-Q⁸-C_(g)(R²⁶R²⁷)—OH  (15)wherein Q⁸ represents a spacer or a direct link; and R⁶, R⁷, R²⁶ and R²⁷and g have the same meanings as defined above; provided that R⁶ and R⁷and P, R²⁶ and/or R²⁷ and C_(g) and Q⁸, R²⁶ and R²⁷ and C_(g), R² or R²⁷and C_(g) and Q⁸ may be combined to form a ring.

In the formula (15), the spacer represented by Q⁸ may also be the samespacer as explained in the above-mentioned Q¹ and Q².

Specific examples of the optically active phosphinoalcohol compoundinclude, for example, optically active compounds shown below:

The bidentate optically active aminothio compound may be an aminothiocompound having an optically active site in its molecule to form anoptically active compound, and includes, for example, an opticallyactive aminothio compound represented by the following formula (16). Theoptically active aminothio compound represented by the following formula(16) is an aminothio compound having an optically active site in itsmolecule.R¹⁸R¹⁹N—C_(f)(R²⁰R²¹)-Q⁹-C_(g)(R²²R²³)—SR²⁸  (16)wherein R²⁸ represents a hydrogen atom, an optionally substitutedhydrocarbon group or an optionally substituted heterocyclic group; Q⁹represents a spacer or a direct link; and R¹⁸, R¹⁹, R²⁰ to R²³ and f andg have the same meanings as defined above; provided that R²⁰ and R²¹ andC_(f), and/or R²² and R²³ and C_(g) may be combined to form a ring; R¹⁸or R¹⁹ and R²⁰ or R²¹ and N and C_(f) may be combined to form a ring;R¹⁸ and R¹⁹ and N may be combined to form a ring such as a heterocyclesuch as a pyridine ring and a piperidine ring; and R²⁰ or R²¹ and C_(f)and Q⁹ and C_(g) and R²² or R²³ may be combined to form a ring such asan aromatic ring and an aliphatic ring.

In the formula (16), the optionally substituted hydrocarbon group andthe optionally substituted heterocyclic group represented by R²⁸ may bethe same respective groups as described above. The spacer represented byQ⁹ may also be the same spacer as explained in the above-mentioned Q¹and Q².

Specific examples of the optically active aminothio compound include,for example, compounds shown below:

The tridentate ligand includes, for example, compounds shown below:

The tetradentate ligand includes, for example, compounds shown below:

Provided that, the above-mentioned chiral ligand used in the presentinvention may be acted as a ligand in a different coordinated statedepending on reaction conditions and the like.

The above-mentioned chiral ligand may be used alone or in a suitablecombination of two or more thereof. These chiral ligands may also becombined arbitrarily with said ligand to form a chiral ligand.

Further, the chiral ligand may be either a commercial product or achiral ligand produced properly by a conventional method or a methoddescribed in literatures described above and the like.

2) Copper Compound

The copper compound used in the present invention may be any coppercompound which can be reacted with a chiral ligand to give a chiralcopper complex, and which does not have a harmful effect in homogeneoushydrogenation when the obtained chiral copper complex is used as thecatalyst for homogeneous hydrogenation.

The copper compound used in the present invention includes a monovalentor divalent copper-containing compound, and includes, for example,copper salt, other copper compound, copper complex and the like.Specific examples of these copper compounds used in the presentinvention include, for example, copper compounds described inOrganocopper Reagent A Practical Approach (OXFORD UNIVERSITY PRESS,1994), and the like.

The copper salt includes, for example, a copper salt represented by thefollowing formula (2-1):[Cu_(n11)X¹ _(n21)]_(n13)  (2-1)wherein X¹s whose number is n12 may be the same or different and eachrepresent an anion; and n11 to n13 independently represent a naturalnumber.

The anion represented by X¹ includes nitrate ion, nitrite ion, halideion, sulfate ion, sulfite ion, sulfonate ion, sulfamate ion, carbonateion, hydroxide ion, carboxylate ion, sulfide ion, thiocyanate ion,phosphate ion, pyrophosphate ion, oxide ion, phosphide ion, chlorateion, perchlorate ion, iodate ion, hexafluorosilicate ion, cyanide ion,borate ion, metaborate ion, borofluoride ion and the like.

The halide ion includes fluoride ion, chloride ion, bromide ion, iodideion and the like.

The sulfonate ion includes a group represented by R¹⁰⁵SO₃ ⁻ (whereinR¹⁰⁵ represents an optionally substituted hydrocarbon group, and theoptionally substituted hydrocarbon group is the same as described above)and the like. Specific examples of the sulfonate ion include, forexample, methanesulfonate ion, benzenesulfonate ion,trifluoromethanesulfonate ion, p-toluenesulfonate ion and the like.

The carboxylate ion includes a group represented by R¹⁰⁶COO⁻ (whereinR¹⁰⁶ represents an optionally substituted hydrocarbon group, and theoptionally substituted hydrocarbon group is the same as describedabove.) and the like. Specific examples of the carboxylate ion include,for example, acetate ion, formate ion, propionate ion, gluconate ion,oleate ion, oxalate ion, benzoate ion, phthalate ion, trifluoroacetateion and the like.

The n11 and n12 independently represent a natural number, preferably anatural number of 1 to 10.

Specific examples of the copper salt include, for example, coppernitrate such as copper(I) nitrate and copper(II) nitrate; copper nitritesuch as copper(I) nitrite and copper(II) nitrite; copper halide such ascopper(I) chloride, copper(II) chloride, copper(I) bromide, copper(II)bromide, copper(I) fluoride, copper(II) fluoride, copper(I) iodide andcopper(II) iodide; copper sulfate such as copper(II) sulfate; coppersulfite such as copper(II) sulfite; copper sulfonate such as copper(I)methanesulfonate, copper (II) methanesulfonate, copper (I)p-toluenesulfonate, copper(II) p-toluenesulfonate, copper(I)trifluoromethanesulfonate and copper (II) trifluoromethanesulfonate;copper sulfamate such as copper(II) sulfamate; copper carbonate such ascopper(II) carbonate; copper hydroxide such as copper(II) hydroxide;copper carboxylate such as copper(I) acetate, copper(II) acetate,copper(II) formate, copper(II) propionate, copper(II) gluconate,copper(II) oleate, copper(II) oxalate, copper(II) benzoate, copper(II)phthalate, copper(II) caprylate, copper(II) citrate, copper(II)salicylate, copper(II) tartrate, copper(II) stearate, coppernaphthenate, copper(II) lactate and copper(II) laurate; copper sulfidesuch as copper(I) sulfide and copper(II) sulfide; copper thiocyanatesuch as copper(I) thiocyanate and copper (II) thiocyanate; copperphosphate such as copper(II) phosphate and copper(II) pyrophosphate;copper oxide such as copper(I) oxide and copper(II) oxide; copperperhalate such as copper(I) chlorate and copper(II) perchlorate; copperhalide such as copper(II) iodate; copper silicate such as copperhexafluorosilicate; copper cyanide such as copper(I) cyanide andcopper(II) cyanide; and copper borate such as copper borate, coppermetaborate and copper tetrafluoroborate; and the like.

Said other copper compound includes, for example, a copper compoundrepresented by the following formula (2-2):[Cu_(n14)X² _(n15)]_(n16)  (2-2)wherein X²s whose number is n15 may be the same or different andrepresent an optionally substituted hydrocarbon group, OR¹⁰¹ (whereinR¹⁰¹ represents an optionally substituted hydrocarbon group), NR¹⁰² ₂(wherein two R¹⁰² may be the same or different and represent a hydrogenatom or an optionally substituted hydrocarbon group), PR¹⁰³ ₂ (whereintwo R¹⁰³ s may be the same or different and represent an optionallysubstituted hydrocarbon group), SR¹⁰⁴ (wherein R¹⁰⁴ represents anoptionally substituted hydrocarbon group) and a 1,3-dicarbonyl compoundor an enolate or hydrido thereof; and n14 to n16 independently representa natural number.

In the formula (2-2), n14 and n15 independently represent a naturalnumber, preferably a natural number of 1 to 10.

The optionally substituted hydrocarbon group represented by X² and theoptionally substituted hydrocarbon groups represented by R¹⁰¹, R¹⁰²,R¹⁰³ and R¹⁰⁴ in OR¹⁰¹, NR¹⁰² ₂, PR¹⁰³ ₂ and SR¹⁰⁴ may be the sameoptionally substituted hydrocarbon group as described above.

Specific examples of OR¹⁰¹ represented by X² include methoxy, ethoxy,n-propoxy, isopropoxy, n-butoxy, s-butoxy, tert-butoxy, phenoxy and thelike.

Specific examples of NR¹⁰² ₂ include dimethylamino, diethylamino,dicyclohexylamino, diphenylamino and the like.

Specific examples of PR¹⁰³ ₂ include dimethylphosphino,diethylphosphino, di(tert-butyl)phosphino, dicyclohexylphosphino,diphenylphosphino and the like.

Specific examples of SR¹⁰⁴ include SMe, SEt, SBu, SPh, S(CH₃C₆H₅) andthe like.

Specific examples of the 1,3-dicarbonyl compound or an enolate thereofinclude 2,5-pentanedione (acac), 1,1,1-trifluoro-2,5-pentanedione,1,1,1,3,3,3-hexafluoropentanedione (hfac), benzoylacetone, methylacetoacetate, ethyl acetoacetate and the like.

Specific examples of the copper compound represented by the formula(2-2) include, for example, copper alkoxide such as copper dimethoxide,copper diethoxide, copper diisopropoxide and copper tert-butoxide;copper phenoxide such as copper phenoxide; copper phosphide such ascopper di(tert-butylphosphide), copper dicyclohexylphosphide and copperdiphenylphosphide; copper amide such as copper dicyclohexylamide; copperthiolate such as copper butanethiolate and copper thiophenolate; copper1,3-dicarbonyl compound or an enolate thereof such ascopper-2,4-pentanedionate, copper benzoylacetonate, copper1,3-diphenyl-1,3-propanedionate, copper ethylacetoacetate, coppertrifluoropentanedionate and copper hexafluoropentanedionate; copperhydride; copper hydrocarbon such as mesityl copper and ethynyl copper;silylated copper such as trimethylsilylethynyl copper; and the like.

Also, other copper compound includes a copper compound represented bythe following formula (2-3):[HCuP(R¹⁰⁷)₃]_(n17)  (2-3)wherein three R¹⁰⁷s are the same or different and represent anoptionally substituted hydrocarbon group; and n17 represents a naturalnumber.

Specific examples of the copper compound represented by the formula(2-3) include, for example, hydrido(triphenylphosphine)copper(I) hexamer(Stryker's reagent) and the like.

Specific examples of the copper compound represented by the formula(2-3) include, for example, copper(I) hydride (triphenylphosphine)hexamer and the like.

The copper compound such as the above-mentioned copper salt and theabove-mentioned other copper compound may form double salt with a saltof an alkali metal (for example, lithium, sodium, potassium, rubidium,caesium and the like) and an alkaline earth metal (for example,magnesium, calcium, strontium, barium and the like). Specific examplesof the formed double salt include, for example, KCuF₃, K₃[CuF₆],CuCN.LiCl, Li₂CuCl₄, Li₂CuCl₃, LiCuBr₂ and the like. These copper saltsand the above-mentioned other copper compounds may be anhydride orhydrate.

The copper complex used as the copper compound include any of a coppercomplex that i) has a ligand other than the chiral ligand, and isreacted with the chiral ligand to form the chiral copper complex capableof using as the catalyst for homogeneous hydrogenation, particularly thecatalyst for homogeneous asymmetric hydrogenation, ii) is a coppercomplex, together with the chiral ligand, capable of using as thecatalyst for homogeneous hydrogenation, particularly the catalyst forhomogeneous asymmetric hydrogenation, or iii) is used as the chiralcopper complex precursor which is reacted with the chiral ligand to formthe chiral copper complex. The above-mentioned copper complex includes,for example, copper complexes described in “Comprehensive OrganometallicChemistry II (Pergamon, 1995)”, “Comprehensive Organometallic Chemistry(Pergamon, 1982)”, “WO2005/016943”, “The Forth Series of ExperimentalChemistry (Jikken Kagaku Kouza 4^(th) edition), Vol. 17 (InorganicComplex/Chelate Complex) and Vol. 18 (Organometallic Complex) 1991,edited by The Chemical Society of Japan (Maruzen)”, “Inorg. Chem., 1382(1965).” and the like.

The copper complex used as the copper compound has a complicatedstructure, and therefore it is not necessarily appropriate to express ina general formula. If the copper complex is daringly expressed by astructural formula, the complexcanbe represented, for example, bythefollowing formula (2-4):[Cu_(n21)L² _(n22)]_(n23)X³ _(n24)  (2-4)wherein L²s whose number is n22 may be the same or different andrepresent a ligand; X³s whose number is n24 may be the same or differentand represent an anion or cation; n21 to n23 independently represent anatural number; and n24 represents 0 or a natural number.

In the formula (2-4), the ligand represented by L² may be a compoundbonded or coordinated to copper. The ligand includes, for example, aligand such as monodentate, bidentate, tridentate, tetradentate and thelike.

Specific examples of the ligand represented by the above-mentioned L²include, for example, a halogen atom, carbon monoxide (CO), nitriles,cyanides, a neutral ligand, hydrocarbon groups, a hydrido group, aphosphorus compound, an amine compound, a sulfur compound, an anion, anoptionally substituted hydrocarbon group, OR¹⁰¹ (R¹⁰¹ is the same asdefined above), NR¹⁰² ₂ (R¹⁰² is the same as defined above), PR¹⁰³ ₂(R¹⁰³ is the same as defined above), SR¹⁰⁴ (R¹⁰⁴ is the same as definedabove), a 1,3-dicarbonyl compound or an enolate thereof (the1,3-dicarbonyl compound and an enolate thereof are the same as definedabove) and the like.

The halogen atom includes fluorine, chlorine, bromine, iodine and thelike.

The nitriles include, for example, nitriles represented by R¹¹⁰CN(wherein R¹¹⁰ represents an optionally substituted hydrocarbon group).The optionally substituted hydrocarbon group represented by R¹¹⁰ is thesame optionally substituted hydrocarbon group as described above.Specific examples of the nitriles include, for example, acetonitrile,benzonitrile and the like.

The cyanides include, for example, cyanides represented by R¹¹¹NC(wherein R¹¹¹ represents an optionally substituted hydrocarbon group).The optionally substituted hydrocarbon group represented by R¹¹¹ is thesame optionally substituted hydrocarbon group as described above.Specific examples of the cyanides include, for example, methylisocyanide, phenyl isocyanide and the like.

The neutral ligand includes, for example, an aromatic compound,hydrocarbons such as olefins and diolefins, other neutral ligands andthe like. The aromatic compound includes benzene, p-cymene,1,3,5-trimethylbenzene (mesitylene), hexamethylbenzene and the like. Theolefins include ethylene, propylene, cyclooctene and the like. Theolefins include butadiene, cyclooctadiene (cod) norbornadiene (nbd) andthe like. Said other neutral ligands include, for example,N,N-dimethylformamide (DMF), acetone, chloroform and the like.

The hydrocarbon groups include cyclopentadienyl (Cp),tetramethylcyclopentadienyl and the like.

The phosphorus compound includes, for example, phosphorus compoundsrepresented by the formula (41):PR¹⁵¹ ₃  (41)wherein three R¹⁵¹s are the same or different and represent a hydrogenatom, an optionally substituted hydrocarbon group, an optionallysubstituted heterocyclic group, an optionally substituted alkoxy group,an optionally substituted aryloxy group, an optionally substitutedaralkyloxy group, an amino group or a substituted amino group.

The optionally substituted hydrocarbon group, the optionally substitutedheterocyclic group, the optionally substituted alkoxy group, theoptionally substituted aryloxy group, the optionally substitutedaralkyloxy group and the substituted amino group, represented by R¹⁵¹,may be the same respective groups as described above.

In the formula (41), the optionally substituted hydrocarbon group, theoptionally substituted heterocyclic group, the optionally substitutedalkoxy group, the optionally substituted aryloxy group, the optionallysubstituted aralkyloxy group and the substituted amino group,represented by R¹⁵¹ may be the same respective groups as describedabove. Also, two phosphorus compounds may be combined with each other toform a diphosphine compound, for example a diphosphine compoundrepresented by the formula (42):R¹⁵¹ ₂P-Q²¹-PR¹⁵¹ ₂  (42)wherein Q²¹ represents a spacer, and four R¹⁵'s may be the same ordifferent and have the same meaning as defined above.

In the formula (42), the spacer represented by Q²¹ is a group derivedfrom R¹⁵¹ and may be the same alkylene group as described above.

Specific examples of the above-mentioned phosphorus compound include,for example, a phosphane compound such as triphenylphosphine,tritolylphosphine, trimethylphosphine, triethylphosphine, methyldiphenylphosphine, dimethyl phenylphosphine, diphenylphosphinomethane(dppm), diphenylphosphinoethane (dppe), diphenylphosphinopropane (dppp),diphenylphosphinobutane (dppb) and diphenylphosphinoferrocene (dppf); aphosphite compound such as trimethyl phosphite, triethyl phosphite andtriphenyl phosphate; and the like.

The amine compound includes, for example, ammonia; aliphatic amines suchas methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine,s-butylamine, tert-butylamine and cyclohexylamine; aromatic amines suchas aniline and dimethylaniline; nitrogen-containing aromaticheterocycles such as pyridine (py) and dimethylaminopyridine,nitrogen-containing aliphatic heterocycles such as pyrrolidine andpiperazine; diamines such as ethylene diamine (en), propylene diamine,triethylene diamine, tetramethylethylene diamine (TMEDA), bipyridine(bpy) and phenanthroline (phen); and the like.

The sulfur compound includes, for example, dimethyl sulfide, diethylsulfide, dipropyl sulfide, dibutyl sulfide and the like.

The anion may be the same anion as X¹ described in the formula (2-1).The optionally substituted hydrocarbon group may also be the sameoptionally substituted hydrocarbon group as described above.

The anion represented by X includes, for example, halide ion, BR¹¹² ₄(four R¹¹²s may be the same or different and represent a hydrogen atom,an optionally substituted hydrocarbon group or a halogen atom), ClO₄,BrO₃, OTf, NO₃, PF₆, SbF₆, AsF₆, I₃, sulfate ion, and CuR¹¹³ ₂ (twoR¹¹³s may be the same or different and represent a halogen atom or anoptionally substituted hydrocarbon group). Herein, Tf represents atrifluoromethanesulfonyl group (SO₂CF₃). The halogen atom, the halideion and the optionally substituted hydrocarbon group are the samerespective groups as described above.

Specific examples of BR¹¹² ₄ include, for example, BH₄, BPh₄, BF₄ andthe like.

Specific examples of CuR¹¹³ ₂ wherein R¹¹³ is the halogen atom include,for example, CuCl₂, CuBr₂, CuI₂, CuF₂ and the like. Specific examples ofCuR¹¹³ ₂ wherein R¹¹³ is the optionally substituted hydrocarbon groupinclude, for example, CuMe₂, CuPh₂, Cu(Mes)₂ and the like. Here, Mesrepresents a mesityl group.

The cation includes an alkali metal ion, an alkaline earth metal ion, anammonium ion, a phosphonium ion and the like.

The alkali metal ion includes, for example, lithium ion, sodium ion,potassium ion, caesium ion and the like.

The alkaline earth metal ion includes, for example, magnesium ion,calcium ion, barium ion and the like.

The ammonium ion includes ammonium ion and a substituted ammonium ion.Specific examples of the substituted ammonium ion include, for example,methylammonium ion, dimethylammonium ion, trimethylammonium ion,tetramethylammonium ion, ethylammonium ion, diethylammonium ion,triethylammonium ion, tetraethylammonium ion, tetrabutylammonium ion,tetraphenylammonium ion and the like.

The phosphonium ion includes phenylphosphonium ion, diphenylphosphoniumion, triphenylphosphonium ion, tetraphenylphosphonium ion and the like.

n21 represents a natural number, preferably a natural number of 1 to 10.n22 represents a natural number, preferably a natural number of 1 to 20.

Specific examples of the copper complex used as the above-mentionedcopper compound include, for example, the following copper compounds asan example:

CuBr—SMe₂, CuI.SMe₂, CuBr.P(OMe)₃, CuI.P(OMe)₃, CuI.P(OEt)₃, CuI.PBu₃,CuO-tert-Bu.PEt₃, CuI.PPh₃, CuBr.(SBu₂)₂, CuI.(SBU₂)₂, CuBr.[P(OMe)₃]₂,CuI.[P(OMe)₃]₂, CuI.TMEDA, CuCl(cod), CuBr(cod), CuI(cod),[Cu(BF₄)(PPh₃)₃], [CuBr(PPh₃)]_(n), Cu(PEt₃)Cp, Cu(PPh₃)CpCu(cod)(hfac),Cu(C₂Me₂)(hfac), [Cu(en)₂] (ClO₄)₂, [Cu(en)₂]SO₄, [CuI(py)],[CuI(MeNC)], [Cu(MeCN)₄][BF₄], [Cu(MeCN)₄][ClO₄], [Cu(bpy)₂][BF₄],[Cu(bpy)₂][ClO₄], [Cu(phen)₂][ClO₄], [Cu(cod)]₂[ClO₄], [Cu(cod)]₂[OTf],[Cu(cod)]₂[BF₄], [Cu(cod)]₂[PF₆], [Cu(CO)(en)][BPh₄], [Cu(NH₃)₄]SO₄,[Cu(py)₄]ClO₄, [Cu(py)₆][ClO₄]₂, [Cu(NH₃)₆]Cl₂, [CuCl(PPh₃)₃],[CuI(PEt₃)₃], CuCl(C₈H₁₂N₂), {[Cu(CNMe)₂][CuI₂]}_(n), K₂[Cu(C₂O₄)₂],(NH₄)₂[CuCl₄], K₃[Cu(CN)₄], K₃[Cu(NO₂)₅], Li[CuMe₂], Li[Cu (C₃H₅)(SPh)],and Cu (NH₄)₂(SO₄)₂.

These copper compounds described above, that is, copper compounds usedas the copper compound such as the copper salt, said other coppercompound, the copper complex may be anhydride or hydrate. These coppercompounds may be used alone or in a suitable combination of two or morethereof.

The above-mentioned copper compound may be either a commercial productor a copper compound produced properly by a conventional method or amethod described in literatures mentioned above in the presentspecification and the like.

3) Chiral Copper Complexes

Specific examples of the chiral copper complex used in the presentinvention include, for example, chiral copper complexes described in“Handbook of Enantioselective Catalysis (VCH, 1993)”, “J. Am. Chem. Soc.2001, 123, 5843”, “J. Org. Chem. 1998, 63, 6090”, “Angew. Chem. Int. Ed.2004, 43, 1679”, “Dalton. Trans. 2003, 1881”, “ORGANIC LETTERS, Vol. 6,No. 14, 2305 (2004)” and the like. The chiral complexes shown below mayalso be included as specific examples of the chiral copper complexhaving the chiral ligand used in the present invention:

L: Bidentate ligand BINAP, SEGPHOS, DM-SEGPHOS, DTBM-SEGPHOS, etc. X¹,X²: Cl, Br, I, F, OTf, OMe, O-t-Bu, H, etc.

L: Monodentate ligand CAMP, MonoPHOS, etc X¹, X²: Cl, Br, I, F, OTf,OMe, O-t-Bu, H, etc. L—CuH L: Bidentate ligand BINAP, SEGPHOS,DM-SEGPHOS, DTBM-SEGPHOS, etc. [L—CuH]_(n) L: Monodentate ligand CAMP,MonoPHOS, etc n: Natural number

L: Bidentate ligand DIPAMP, CHIRAPHOS, PROPHOS, BINAP, etc. X: Cl, Br,I, F, OTf, ClO₄, BF₄, PF₆, AsF₆, SbF₆, etc. [L—Cu—L] X L: Bidentateligand BINAP, SEGPHOS, DM-SEGPHOS, DTBM-SEGPHOS, etc. X: Cl, Br, I, F,OTf, ClO₄, BF₄, PF₆, AsF₆, SbF₆, etc. [L—Cu—L²] X L: Bidentate ligandBINAP, SEGPHOS, DM-SEGPHOS, DTBM-SEGPHOS, etc. L²: cod, nbd, etc. X: Cl,Br, I, F, OTf, ClO₄, BF₄, PF₆, AsF₆, SbF₆, etc.

L: Bidentate ligand BINAP, SEGPHOS, DM-SEGPHOS, DTBM-SEGPHOS, etc. L²:MeCN, CO, H₂O, NH₃, etc. X: Cl, Br, I, F, OTf, ClO₄, BF₄, PF₆, AsF₆,SbF₆, etc.

L: Bidentate ligand BINAP, SEGPHOS, DM-SEGPHOS, DTBM-SEGPHOS, etc.

L: Bidentate ligand DPEN, DAIPEN, BINAP, SEGPHOS, etc. X: Cl, Br, I, F,OTf, ClO₄, BF₄, PF₆, AsF₆, SbF₆, etc. L—Cu L: Tetradentate ligand TROSTLIGAND, Jacobsen Ligand, etc. [L—Cu] X L: Tetradentate ligand TROSTLIGAND, Jacobsen Ligand, etc. X: Cl, Br, I, F, OTf, ClO₄, BF₄, PF₆,AsF₆, SbF₆, etc.

These chiral copper complexes may be used alone or, if necessary, in asuitable combination of two or more thereof. The chiral copper complexhaving the chiral ligand may also be anhydride or hydrate. The chiralcopper complex used in the present invention may be either a commercialproduct or a chiral copper complex produced properly by a conventionalmethod, a method described in literatures mentioned above or a methoddescribed later and the like.

The chiral copper complex used in the present invention may be anychiral copper complex having the chiral ligand as explained in “1)Chiral ligand” mentioned above. The chiral copper complex has acomplicated structure, and therefore it is not necessarily appropriateto express in a general formula. If the copper complex is daringlyexpressed by a structural formula, the complex can be represented, forexample, by the following formula (1):[Cu_(n1)L¹ _(n2)L² _(n3)X¹ _(n5)X² _(n6)H_(n9)]_(n4)[X¹ _(n5)X³_(n7)]_(n8)  (1)wherein L¹s whose number is n2 may be the same or different and eachrepresent a chiral ligand; L²S whose number is n3 may be the same ordifferent and represent a ligand; X¹s whose number is n5 may be the sameor different and represent an anion; X²s whose number is n6 may be thesame or different and represent an optionally substituted hydrocarbongroup, OR¹⁰¹ (wherein R¹⁰¹ represents an optionally substitutedhydrocarbon group), NR¹⁰² ₂ (wherein two R¹⁰²S may be the same ordifferent and represent an optionally substituted hydrocarbon group),PR¹⁰³ ₂ (wherein two R¹⁰³s may be the same or different and represent anoptionally substituted hydrocarbon group), SR¹⁰⁴ (wherein R¹⁰⁴represents an optionally substituted hydrocarbon group) or a1,3-dicarbonyl compound or an enolate or hydride thereof; X³s whosenumber is n7 may be the same or different and represent an anion or acation; n1, n2 and n4 independently represent a natural number; n3 andn6 to n9 independently represent 0 or a natural number; and two n5s maybe the same or different and represent 0 or a natural number.

In the formula (1), the chiral ligand represented by L¹ is the chiralligand as explained in “1) Chiral ligand” mentioned above. The ligandrepresented by L², the anion represented by X¹, the optionallysubstituted hydrocarbon group, OR¹⁰¹, NR¹⁰² ₂, PR¹⁰³ ₂, SR¹⁰⁴ and the1,3-dicarbonyl compound or the enolate thereof represented by X², andthe anion and the cation represented by X³ may be the same as describedabove, respectively.

The n1 represents a natural number, preferably a natural number of 1 to10. Then 2 represents a natural number, preferably a natural number of 1to 12. The n3 represents 0 or a natural number, preferably 0 or anatural number of 1 to 20. The n5 represents a natural number,preferably a natural number of 1 to 10. The n6 represents 0 or a naturalnumber, preferably 0 or a natural number of 1 to 10.

The above-mentioned chiral copper complex represented by the formula (1)includes, for example, a chiral copper complex represented by theformula (61):[L¹¹L¹²CuL¹³]_(n35)  (61)wherein L¹¹ represents a bidentate optically active phosphorus compound;L¹² represents a phosphorus compound different from L¹¹; L¹³ representsa ligand; and n35 represents a natural number.

In the formula (61), the bidentate optically active phosphorus compoundrepresented by L¹¹ may be the same optically active phosphorus compoundas explained in the above-mentioned Chiral ligand. The bidentateoptically active phosphorus compound represented by L¹¹ is particularlypreferably an optically active diphosphine compound. The above-mentionedoptically active diphosphine compound may be the same optically activephosphorus compound as explained in the above-mentioned Chiral ligand.The phosphorus compound different from L¹¹, represented by L¹², may beany phosphorus compound different from the bidentate optically activephosphorus compound represented by L¹¹, or may be an optically activeform (a chiral ligand) or a non-chiral ligand, and, for example, may bethe same optically active phosphorus compound as explained in theabove-mentioned Chiral ligand or the phosphorus compound as explained inthe ligand represented by L² in the above-mentioned formula (2-4) in thepresent specification. The ligand represented by L¹³ may be the sameligand as explained in the ligand represented by L² in theabove-mentioned formula (2-4).

Specific examples of the chiral copper complex represented by theformula (61) include, for example, [CuF(PPh₃)(L²⁰)]_(n),[CuCl(PPh₃)(L²⁰)]_(n), [CuBr(PPh₃)(L²⁰)]_(n), [CuI(PPh₃)(L²⁰)]_(n),[CuH(PPh₃)(L²⁰)]_(n), [CuOTf(PPh₃)(L²⁰)]_(n), [Cu(NO₃)(PPh₃)(L²⁰)]_(n),[Cu(OAc)(PPh₃)(L²⁰)]_(n), [CuCl(P(3,5-xylyl)₃)(L²⁰)]_(n) and the like;

wherein L²⁰ represents the same optically active diphosphine compound asthat of L¹¹: ((R)-BINAP, (S)-BINAP, (R)-DM-BINAP, (S)-DM-BINAP,(R)-SEGPHOS, (S)-SEGPHOS, (R)-DM-SEGPHOS, (S)-DM-SEGPHOS,(R)-DTBM-SEGPHOS, (S)-DTBM-SEGPHOS, (R,R)-SKEWPHOS, (S,S)-Me-DuPHOS,(S,S)-Me-DuPHOS, (R,S)-Josiphos, (S,R)-Josiphos and the like); and nrepresents a natural number.

The chiral copper complex used in the present invention may be, forexample, produced based on a method described in the literatures in thepresent specification and the like.

That is, the chiral copper complex can be easily obtained by reactingthe chiral ligand with the copper compound, in a suitable solvent ifnecessary.

The amount of the chiral ligand and the copper compound used are notparticularly limited because it varies depending on the kind of thecopper compound and the chiral ligand used and the like. The amount ofthe chiral ligand used is suitably selected usually in the range of0.000001 to 100 equivalents, preferably 0.00001 to 10 equivalentsrelative to the copper compound.

The solvent used as necessary includes, for example, aliphatichydrocarbons such as pentane, hexane, heptane, octane, decane andcyclohexane; aromatic hydrocarbons such as benzene, toluene and xylene;halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane,chloroform, carbon tetrachloride and o-dichlorobenzene; ethers such asdiethyl ether, diisopropyl ether, tert-butyl methyl ether,dimethoxyethane, ethylene glycol diethyl ether, tetrahydrofuran,1,4-dioxane and 1,3-dioxolane; alcohols such as methanol, ethanol,2-propanol, n-butanol, s-butanol, tert-butanol, 2-ethoxyethanol andbenzyl alcohol; ketones such as acetone, methyl ethyl ketone, methylisobutyl ketone and cyclohexanone; esters such as methyl acetate, ethylacetate, n-butyl acetate and methylpropionate; amides such as formamide,N,N-dimethylformamide and N,N-dimethylacetamide; sulfoxides such asdimethyl sulfoxide; cyano-containing organic compounds such asacetonitrile; N-methylpyrrolidone; water and the like. These solventsmay be used alone or in a suitable combination of two or more thereof.

The amount of the solvent used is suitably selected usually in the rangeof 1 to 1000 times by volume, preferably 5 to 200 times by volumerelative to the copper compound.

The reaction of the chiral ligand and the copper compound may be carriedout in the presence of other reagent, if necessary.

Said other reagent includes an acid, a base, a reducing agent, ahalogenating agent and the like.

The acid includes an inorganic acid, an organic acid, a Lewis acid andthe like.

The inorganic acid includes, for example, hydrochloric acid, hydrobromicacid, sulfuric acid, phosphoric acid, tetrafluoroboric acid, perchloricacid, periodic acid and the like.

The organic acid includes, for example, carboxylic acid such as formicacid, acetic acid, valeric acid, hexanoic acid, citric acid,chloroacetic acid, dichloroacetic acid, trichloroacetic acid,trifluoroacetic acid, benzoic acid, salicylic acid, oxalic acid,succinic acid, malonic acid, phthalic acid, tartaric acid, malic acidand glycolic acid; sulfonic acid such as methanesulfonic acid,benzenesulfonic acid, p-toluenesulfonic acid andtrifluoromethanesulfonic acid; and the like.

The Lewis acid includes, for example, aluminum halide such as aluminumchloride and aluminum bromide; dialkylaluminum halide such asdiethylaluminum chloride, diethylaluminum bromide anddiisopropylaluminum chloride; trialkoxy aluminum such as triethoxyaluminum, triisopropoxy aluminum, and tri-tert-butoxy aluminum; titaniumhalides such as titanium tetrachloride; tetraalkoxy titanium such astetraisopropoxy titanium; boron halide such as boron trifluoride, borontrichloride, boron tribromide and boron trifluoride-diethyl ethercomplex; zinc halide such as zinc chloride and zinc bromide; and thelike.

The base includes an inorganic base, an organic base and the like. Theinorganic base includes, for example, alkali metal hydroxides such aslithium hydroxide, sodium hydroxide and potassium hydroxide; metalcarbonates such as sodium carbonate, potassium carbonate, magnesiumcarbonate and calcium carbonate; metal hydrogen carbonates such assodium hydrogen carbonate and potassium hydrogen carbonate; metalhydrides such as lithium hydride, sodium hydride and potassium hydride;ammonia, and the like. The organic base includes, for example, alkalimetal-alkaline earth metal salts such as lithium methoxide, lithiumethoxide, lithium-tert-butoxide, sodium methoxide, sodium ethoxide,sodium tert-butoxide, potassium methoxide, potassium ethoxide, potassiumtert-butoxide, potassium naphthalenide, sodium acetate, potassiumacetate, magnesium acetate, calcium acetate, lithium diethylamide,lithium diisopropylamide, lithium bis(trimethylsilyl)amide, sodiumbis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, lithiumdiphenylphosphide, sodium diphenylphosphide and potassiumdiphenylphosphide; organic amines such as triethylamine,diisopropylethylamine, N,N-dimethylaniline, piperidine, pyridine,4-dimethylaminopyridine, 1,5-diazabicyclo[4.3.0]non-5-ene,1,8-diazabicyclo[5.4.0]undec-7-ene, tri-n-butylamine andN-methylmorpholine; organometallic compounds such as methyl lithium,ethyl lithium, n-propyl lithium, isopropyl lithium, n-butyl lithium,s-butyl lithium, tert-butyl lithium, phenyl lithium, methyl magnesiumchloride, ethyl magnesium chloride, n-propyl magnesium chloride,isopropyl magnesium chloride, n-butyl magnesium chloride, s-butylmagnesium chloride, tert-butyl magnesium chloride, phenyl magnesiumchloride, methyl magnesium bromide, ethyl magnesium bromide, n-propylmagnesium bromide, isopropyl magnesium bromide, n-butyl magnesiumbromide, s-butyl magnesium bromide, tert-butyl magnesium bromide andphenyl magnesium bromide; the optically active forms of the diaminecompounds exemplified above as the chiral ligand (the optically activediamine compound) and racemic form thereof; and the like.

The reducing agent includes, for example, lithium aluminum hydride,sodium borohydride and the like.

The halogenating agent includes, for example, a quaternary ammonium saltsuch as tetrabutylammonium fluoride, tetrabutylammonium bromide andtetrabutylammonium triphenyl difluorosilicate; a halogen such as iodineand bromine; and the like.

These other reagents may be used alone or in a suitable combination oftwo or more thereof.

The amount of said other reagents used is suitably selected usually inthe range of 0.001 to 100 equivalents, preferably 0.01 to 100equivalents relative to the copper compound.

The reaction temperature of the chiral ligand with the copper compoundvaries depending on the kind of the solvent and the like. Thetemperature is suitably selected usually in the range of −100° C. to150° C., preferably −80° C. to 120° C.

The reaction time is suitably selected usually in the range of 1 minuteto 100 hours, preferably 10 minutes to 24 hours.

After the reaction, the obtained chiral copper complex may be used as itstands without post-treatment and the like and as the catalyst forhomogeneous hydrogenation, particularly the catalyst for homogeneousasymmetric hydrogenation, or may be used as said catalyst after carryingout with post-treatment, purification, isolation and the like, ifnecessary. Specific a method of the post-treatment include separationand purification of a method known per se, such as solvent extraction,salting out, crystallization, recrystallization, various kinds ofchromatography and the like.

There are some cases where thus obtained chiral copper complex may be amixture of so-called monomer and(or) polymer. That is, there are somecases where thus obtained chiral copper complex may be mixed with thechiral copper complexes of the above-mentioned formula (1) wherein n4 is1 (monomers) and the chiral copper complexes of the above-mentionedformula (1) wherein n4 is 2 or more (polymers).

[1-2] Catalyst for Homogeneous Hydrogenation

The catalyst for homogeneous hydrogenation containing the chiral coppercomplex and the catalyst for homogeneous hydrogenation containing themixture of the chiral ligand and the copper compound of the presentinvention may be a solid or liquid state, and may be added othercomponents to said catalyst. Said other components added as necessarymay be any components which does not have a harmful effect inhomogeneous hydrogenation, and include, for example, the solvent, saidother reagents and the like mentioned above.

In the catalyst for homogeneous hydrogenation containing the mixture ofthe chiral ligand and the copper compound of the present invention, amixing ratio of the chiral ligand and the copper compound may besuitably selected such that the copper compound is usually used in therange of 0.000001 to 10 equivalents, preferably 0.0001 to 1 equivalentrelative to the chiral ligand.

[2] Process for Producing a Hydrogenated Compound of an unsaturatedCompound

The process for producing a hydrogenated compound of an unsaturatedcompound of the present invention can be carried out by hydrogenation ofan unsaturated compound as a starting material (substrate) in ahomogeneous system in the presence of the catalyst for homogeneoushydrogenation to give a desired hydrogenated compound of the unsaturatedcompound, which is easily and with a good yield. Here, when a prochiralcompound is used as the unsaturated compound and the catalyst forhomogeneous asymmetric hydrogenation is used as the catalyst forhomogenous hydrogenation, the resulting hydrogenated compound of theunsaturated compound can be obtained as an optically active compoundthereof.

In the production process of the present invention, the homogeneoushydrogenation may be carried out in the presence of the above-mentionedcopper complex or may be carried out by mixing the chiral ligand and thecopper compound with the unsaturated compound.

Also, the production process of the present invention may be carried outby further adding the catalyst for homogeneous hydrogenation containingthe copper complex having the chiral ligand, the catalyst forhomogeneous hydrogenation containing the mixture of the chiral ligandand the copper compound, the chiral ligand and/or the copper compound,if necessary, to the reaction system (the reaction mixture).

1) Unsaturated Compound

The unsaturated compound used in the present invention includes, forexample, an unsaturated compound such as an alkene, a ketone, an imine,a ketocarboxylic acid, a ketoalkene and the like.

The alkene is preferably a prochiral alkene and includes, for example,an alkene represented by the following formula (21):

The ketone is preferably a prochiral ketone and includes, for example, aketone represented by the following formula (22)

The imine is preferably a prochiral imine and includes, for example, animine represented by the following formula (23)

The ketocarboxylic acid is preferably a prochiral ketocarboxylic acidand include, for example, a ketocarboxylic acid represented by thefollowing formula (24):

The ketoalkene is preferably a prochiral ketoalkene and include, forexample, a ketoalkene represented by the following formula (25):

In the above-mentioned formulae (21) to (25), the groups represented byR³¹ to R⁴⁵ may be such groups that the respective compounds can existand include, for example, the groups suitably selected from a hydrogenatom, an optionally substituted hydrocarbon group, an optionallysubstituted heterocyclic group, a halogen atom, a halogenatedhydrocarbon group, an optionally substituted alkoxy group, an optionallysubstituted aryloxy group, an optionally substituted aralkyloxy group,an optionally substituted heteroaryloxy group, an optionally substitutedalkylthio group, an optionally substituted arylthio group, an optionallysubstituted aralkylthio group, an optionally substituted heteroarylthiogroup, an optionally substituted acyl group, an optionally substitutedacyloxy group, an optionally substituted alkoxycarbonyl group, anoptionally substituted aryloxycarbonyl group, an optionally substitutedaralkyloxycarbonyl group, an optionally substituted alkylenedioxy group,a nitro group, an amino group, a substituted amino group, a cyano group,a sulfo group, a substituted silyl group, a substituted silyloxy group,a hydroxy group, a carboxy group, an optionally substitutedalkoxythiocarbonyl group, an optionally substituted aryloxythiocarbonylgroup, an optionally substituted aralkyloxythiocarbonyl group, anoptionally substituted alkylthiocarbonyl group, an optionallysubstituted arylthiocarbonyl group, an optionally substitutedaralkylthiocarbonyl group, an optionally substituted carbamoyl group, asubstituted phosphino group, an aminosulfonyl group, an alkoxysulfonylgroup and the like. In the formulae (24) and (25), Q¹¹ and Q¹² representa spacer or a direct link. Provided that, R³¹ and R³², R³¹ and R³³, R³¹and R³⁴, R³² and R³³, R³² and R³⁴, R³³ and R³⁴, R³⁵ and R³⁶, R³⁸ andR³⁹, R³⁸ or R³⁹ and R³⁷, R⁴⁰ and Q¹¹, R⁴⁰ and R⁴¹, R⁴¹ and Q¹¹, R⁴² andQ¹², R⁴⁴ and Q¹², R² and R⁴³, R⁴² and R⁴⁴ or R⁴⁵, R⁴³ and R⁴⁴, R⁴³ andR⁴⁵, or R⁴⁴ and R⁴⁵ may be combined with each other to form a ring. Saidformed ring includes, for example, the ring(s) formed by bonding throughan alkylene group or an alkylenedioxy group. Provided that, these formedrings may have further substituents.

In the above-mentioned formulae (21) to (25), the respective groupsrepresented by R³¹ to R⁴⁵ and the alkylene or alkylenedioxy group whenthe ring(s) is/are formed may be the same respective groups as explainedin the above-mentioned [1] and the respective groups as explained in thesubstituent, or respective groups described later unless otherwisespecified (The same applies hereinafter). The spacer represented by Q¹¹and Q¹² may also the same spacer as explained in the above-mentioned[1].

Also, in the formula (24), the group represented by R⁴¹ may be a metalatom such as an alkali metal and the like. The above-mentioned carboxygroup and sulfo group may also form a metal salt of a metal atom such asan alkali metal and the like. The alkali metal includes lithium, sodium,potassium, rubidium, caesium and the like.

In the formulae (21) to (25) when the respective groups of R³¹ to R⁴⁵forms ring(s), that is, for example, when R³¹ and R³², R³¹ and R³³, R³²and R³⁴, R³³ and R³⁴, R³⁵ and R³⁶, R³⁸ and R³⁹, R³⁸ or R³⁹ and R³⁷, R⁴⁰and Q¹¹, R⁴⁰ and R⁴¹, R⁴¹ and Q¹¹, R⁴² and Q¹², R⁴² and R⁴³, R⁴³ and R⁴²or R⁴⁵, R⁴³ and R⁴⁴, or R⁴⁴ and R⁴⁵ are combined with each other to forma ring, the formed ring include, for example, a ring formed by bondingthrough a carbon chain such as the optionally substituted alkylenegroup, the optionally substituted alkylenedioxy group and the like. Theformed ring may be a monocyclic, polycyclic or fused ring and includes,for example, an aliphatic ring, an aromatic ring, and the like, such asa 4- to 8-membered ring and the like.

The optionally substituted alkylene group includes an alkylene group anda substituted alkylene group. The alkylene group may be linear orbranched and includes, for example, an alkylene group having 1 to 10carbon atom(s). Specific examples of the alkylene group include, forexample, methylene, ethylene, propylene, trimethylene, tetramethylene,pentamethylene, hexamethylene, heptamethylene, octamethylene,nonamethylene, decamethylene, 2-methylpropylene, 2,2-dimethylpropylene,2-ethylpropylene and the like. A carbon chain of the forming ring maycontain an oxygen atom, a sulfur atom, an imino group,asubstitutediminogroup, acarbonylgroup (C═O), athiocarbonyl group (C═S)and the like. When the ring is formed, specific examples of the ringinclude a cyclopentane ring, a cyclohexane ring, for example a 5- to7-membered lactone ring, for example, a 5- to 7-membered lactam ring,cyclopentanone ring and cyclohexanone ring. These formed rings may berings that a carbon atom at a moiety to be asymmetrically hydrogenatedcan become an asymmetric carbon atom by homogeneous asymmetrichydrogenation. A substituent on the substituted imino group is the samesubstituent as described above.

The substituted alkylene group (an alkylene group having a substituent)includes an alkylene group wherein at least one hydrogen atom of theabove-mentioned alkylene group is substituted with a substituent.

The optionally substituted alkylenedioxy group includes an alkylenedioxygroup and a substituted alkylenedioxy group. The alkylenedioxy groupincludes, for example, an alkylenedioxy group having 1 to 3 carbonatom(s). Specific examples of the alkylenedioxy group include, forexample, methylenedioxy, ethylenedioxy, trimethylenedioxy,propylenedioxyand the like.

The substituted alkylenedioxy group (an alkylenedioxy group having asubstituent) includes an alkylenedioxy group wherein at least onehydrogen atom of the above-mentioned alkylenedioxy group is substitutedwith a substituent. Specific examples of the substituted alkylenedioxygroup include difluoromethylenedioxy and the like.

The spacer includes an optionally substituted divalent organic groupsuch as an alkylene group, an arylene group, a heteroarylene group andthe like. The above-mentioned divalent organic group may have at leastone heteroatom or heteroatomic group such as an oxygen atom, a carbonylgroup, a sulfur atom, an imino group, a substituted imino group and thelike in an arbitrary position of at the terminal position or in thechain of said organic group. A substituent on the substituted iminogroup is the same a substituent as described later.

The alkylene group includes, for example, an alkylene group having 1 to10 carbon atom(s). Specific examples of the alkylene group include, forexample, methylene, ethylene, trimethylene, propylene, tetramethylene,pentamethylene, hexamethylene, heptamethylene, octamethylene,nonamethylene, decamethylene and the like.

The arylene group includes, for example, an arylene group having 6 to 20carbon atoms. Specific examples of the arylene group include, forexample, phenylene, biphenyldiyl, binaphthalenediyl, bisbenzodioxolediyland the like.

The heteroarylene group includes, for example, a heteroarylene grouphaving 2 to 20 carbon atoms and a 3- to 8-membered, preferably 5- to6-membered monocyclic, polycyclic or fused ring heteroarylene groupcontaining at least 1, preferably 1 to 3 heteroatom(s) such as anitrogen atom, an oxygen atom and/or a sulfur atom. Specific examples ofthe heteroarylene group include, for example, bipyridinediyl,bisbenzothioldiyl, bisthioldiyl and the like.

The divalent organic group having the heteroatom or the heteroatomicgroup includes —CH₂—O—CH₂, —C₆—H₄—O—C₆H₄— and the like.

These divalent organic groups may be substituted with the substituent asexplained in the above-mentioned [1].

In the formula (24), the group represented by R⁴¹ may be a metal atomsuch as an alkali metal and the like. The carboxy group and the sulfogroup may also form a metal salt of a metal atom such as an alkali metaland the like. The alkali metal includes lithium, sodium, potassium,rubidium, caesium and the like.

These unsaturated compounds are particularly preferably prochiralcompounds. Provided that, when the unsaturated compound is the prochiralcompound, the groups represented by R³¹ to R⁴⁵ in the above-mentionedformulae (21) to (25) may be such groups that the resulting hydrogenatedcompound of the prochiral compound is capable of forming the opticallyactive compound.

Specific examples of the alkene of the unsaturated compounds used in thepresent invention include, for example, alkenes shown below:

Specific examples of the ketone include, for example, methyl ethylketone, acetophenone, 1-indanone, 3,4-dihydro-(2H)-naphthalenoneferrocenyl methyl ketone and the like, and include, for example, ketonesshown below:

Specific examples of the imine include, for example, imines shown below:

Specific examples of the ketocarboxylic acid include, for example,ketocarboxylic acids shown below:

Specific examples of the ketoalkene include, for example, ketoalkenesshown below:

Provided that, the above-mentioned unsaturated compound may further havea chiral center in a molecule thereof in addition to a moiety formingitself prochiral.

2) Homogeneous hydrogenation (Homogeneous asymmetric hydrogenation)

In the present invention, the homogeneous hydrogenation (homogenoushydrogenation method) is carried out in the presence of a hydrogensource. The hydrogen source includes hydrogen gas and a hydrogen donor.That is, the homogeneous hydrogenation in the present invention is ahomogeneous hydrogenation carried out in the presence of hydrogen gas(preferably a homogeneous asymmetric hydrogenation) or a homogeneoustransfer hydrogenation carried out in the presence of the hydrogen donor(preferably a homogeneous asymmetric transfer hydrogenation).

The amount of the catalyst for homogeneous hydrogenation used is notparticularly limited. When the catalyst for homogeneous hydrogenationcontaining the chiral copper complex is used, the amount of the chiralcopper complex used is suitably selected in the range of 0.00001 to 1equivalent, preferably 0.0001 to 0.1 equivalents relative to theunsaturated compound. Also, when the catalyst for homogeneoushydrogenation containing the mixture of the chiral ligand and the coppercompound is used, the amount of the copper compound used is suitablyselected in the range of 0.00001 to 1 equivalent, preferably 0.0001 to0.1 equivalents relative to the unsaturated compound.

A pressure of the hydrogen gas, in the case of in which the productionprocess of the present invention is carried out in the presence of thehydrogen gas by the homogeneous hydrogenation, preferably thehomogeneous asymmetric hydrogenation is sufficient in such a conditionof hydrogen atmosphere or the pressure of 0.1 MPa or less. The pressure,in consideration of economically, operativity and the like, is suitablyselected usually in the range of 0.1 to 20 MPa, preferably 0.2 to 10MPa. Further, it is possible to maintain a high activity even at 1 MPaor less in consideration of economic efficiency.

The hydrogen donor includes, for example, formic acid or formates, acombination of formic acid and a base, hydroquinone, cyclohexadiene,phosphorous acid, an alcohol and the like. These compounds areparticularly preferably formic acid or formates, a combination of formicacid and a base, the alcohol and the like.

The formates in formic acid and formates include a metal salt of formicacid such as an alkali metal formate and an alkaline earth metalformate, an ammonium salt, a substituted amine salt and the like.

Formic acid in the combination of formic acid and the base may be suchformic acid as to form a formate or to substantially form a formate in areaction system.

The base forming the metal formates such as alkali metal formates andalkaline earth metal formate, ammonium salt, the substituted amine salt;and the base in a combination of formic acid and a base, includeammonia, an inorganic base, an organic base and the like.

The alkali metal forming formates include lithium, sodium, potassium,rubidium, caesium and the like. The alkaline earth metals includemagnesium, calcium, strontium, barium and the like.

The inorganic base includes, for example, the alkali metal salt or analkaline earth metal salt such as potassium carbonate, potassiumhydroxide, lithium hydroxide, sodium hydrogen carbonate, sodiumcarbonate, potassium hydrogen carbonate, sodium hydroxide, magnesiumcarbonate and calcium carbonate; metal hydrides such as sodium hydride;and the like.

The organic base includes, for example, alkali metal alkoxides such aspotassium methoxide, sodium methoxide, lithium methoxide, sodiumethoxide, potassium isopropoxide, lithium tert-butoxide, sodiumtert-butoxide and potassium tert-butoxide, alkali metal acetates oralkaline earth metal acetates such as sodium acetate, potassium acetate,magnesium acetate and calcium acetate; organic amines such astriethylamine, diisopropylethylamine, N,N-dimethylaniline, piperidine,pyridine, 4-dimethylaminopyridine, 1,5-diazabicyclo[4.3.0]non-5-ene,1,8-diazabicyclo[5.4.0]undec-7-ene, tri-n-butylamine andN-methylmorpholine; organometallic compounds such as methyl magnesiumbromide, ethyl magnesium bromide, propyl magnesium bromide, tert-butylmagnesium chloride, tert-butyl magnesium bromide, methyl lithium, ethyllithium, propyl lithium, n-butyl lithium and tert-butyl lithium; and thelike.

The alcohol as the hydrogen donor is preferably lower alcohols having ahydrogen atom at the α-position, and specific examples include, forexample, methanol, ethanol, n-propanol, isopropanol, n-butanol,sec-butanol and the like. The alcohol as the hydrogen donor isparticularly preferably propanol.

The amount of the hydrogen donor used is suitably selected usually inthe range of 0.1 to 10000 equivalents, preferably 0.5 to 2000equivalents, relative to the unsaturated compound.

The homogeneous hydrogenation in the present invention, that is, theprocess for producing a hydrogenated compound of an unsaturatedcompound, can be carried out in a solvent if necessary. The solventincludes, for example, aromatic hydrocarbons such as benzene, tolueneand xylene; aliphatic hydrocarbons such as pentane, hexane, heptane andoctane; halogenated hydrocarbons such as dichloromethane, chloroform,carbon tetrachloride and dichloroethane; ethers such as diethyl ether,diisopropyl ether, tert-butyl methyl ether, cyclopentyl methyl ether,dimethoxyethane, tetrahydrofuran, dioxane and dioxolane; alcohols suchas methanol, ethanol, 2-propanol, n-butanol, tert-butanol and benzylalcohol; polyhydric alcohols such as ethylene glycol, propylene glycol,1,2-propanediol and glycerin; amides such as N,N-dimethylformamide andN,N-dimethylacetamide; ketones such as acetone and methyl isobutylketone; esters such as methyl acetate, ethyl acetate and butyl acetate;acetonitrile; N-methylpyrrolidone; dimethyl sulfoxide; water and thelike. These solvents may be used alone or in a suitable combination oftwo or more thereof.

The amount of the solvent used is not particularly limited and variesdepending on economical efficiency and the kind and solubility of theunsaturated compound used as a reaction substrate, and is suitablyselected usually for example in a ratio of 0 to 200, preferably 0 to 40,relative to the reaction substrate. For example, when an alcohol is usedas the solvent, the reaction can be carried out in the solvent at a lowconcentration of 1% or less or in a solvent-free or nearly solvent-freestate, depending on the unsaturated compound used.

The reaction temperature is not particularly limited and variesdepending on the kind and amount of the asymmetric catalyst and the kindof the unsaturated compound, and is suitably selected usually in therange of −30 to 250° C., preferably 0 to 100° C., in consideration ofeconomical efficiency. For example, the reaction can be carried out evenat a low temperature of −30 to 0° C. or at a high temperature of 100 to250° C.

The reaction time varies depending on the kind and amount of theasymmetric catalyst used, the kind and concentration of the unsaturatedcompound used, and reaction conditions such as reaction temperature andhydrogen pressure, and is suitably selected usually in the range of 1minute to 48 hours, preferably 10 minutes to 24 hours.

The homogeneous hydrogenation in the present invention can be carriedout regardless of whether the reaction form is batch-wise or continuous.The reaction can be carried out in reaction containers known in the art,such as a flask, a reactor, an autoclave and the like.

The homogeneous hydrogenation can be carried out if necessary in thepresence of an additive. The additive include an acid, afluorine-containing alcohol, a base, a quaternary ammonium salt, aquaternary phosphonium salt, a phosphorus compound, a halogen, areducing agent, water and the like.

The acid as the additive includes an inorganic acid, an organic acid,Lewis acid and the like.

The inorganic acid includes, for example, hydrochloric acid, hydrobromicacid, sulfuric acid, phosphoric acid, tetrafluoroboric acid, perchloricacid, periodic acid and the like.

The organic acid includes, for example, carboxylic acids such as formicacid, acetic acid, valeric acid, hexanoic acid, citric acid,chloroacetic acid, dichloroacetic acid, trichloroacetic acid,trifluoroacetic acid, benzoic acid, salicylic acid, oxalic acid,succinic acid, malonic acid, phthalic acid, tartaric acid, malic acidand glycolic acid; sulfonic acids such as methanesulfonic acid,benzenesulfonic acid, p-toluenesulfonic acid andtrifluoromethanesulfonic acid; and the like.

Lewis acid includes, for example, aluminum halides such as aluminumchloride and aluminum bromide; dialkylaluminum halides such asdiethylaluminum chloride, diethylaluminum bromide anddiisopropylaluminum chloride; trialkoxy aluminum such as triethoxyaluminum, triisopropoxy aluminum, and tri-tert-butoxy aluminum; titaniumhalides such as titanium tetrachloride; tetraalkoxy titanium such astetraisopropoxy titanium; boron halides such as boron trifluoride, borontrichloride, boron tribromide, and a boron trifluoride-diethyl ethercomplex; zinc halides such as zinc chloride and zinc bromide; and thelike.

These acids may be used alone or in a suitable combination of two ormore thereof.

The amount of the acid used is suitably selected usually in the range of0.0001 to 100 equivalents, preferably 0.001 to 10 equivalents, relativeto the unsaturated compound.

The fluorine-containing alcohol as the additive is preferably afluorine-containing aliphatic alcohol. Specific examples of thefluorine-containing alcohol include a saturated or unsaturatedfluorine-containing aliphatic alcohol having 1 to 10 carbon atoms.Specific examples of the fluorine-containing aliphatic alcohol include,for example, 2,2,2-trifluoroethanol, 2,2-difluoroethanool,3,3,3-trifluoropropanol, 2,2,3,3,3-pentafluoropropanol,2,2,3,3-tetrafluoropropanol, 3,3,4,4,4-pentafluorobutanol,4,4,5,5,5-pentafluoropentanol, 5,5,6,6,6-pentafluorohexanol,3,3,4,4,5,5,6,6,6-nonafluorohexanol, 1,1,1,3,3,3-hexafluoro-2-propanoland the like. These fluorine-containing aliphatic alcohols may be usedalone or in a suitable combination of two or more thereof.

The amount of the fluorine-containing alcohol used is suitably selectedusually in the range of 0.01 to 100 equivalents, preferably 0.1 to 10equivalents, relative to the unsaturated compound.

The base as the additive includes an inorganic base, an organic base andthe like. The inorganic base includes, for example, alkali metalhydroxides such as lithium hydroxide, sodium hydroxide and potassiumhydroxide; metal carbonates such as sodium carbonate, potassiumcarbonate, magnesium carbonate and calcium carbonate; metal hydrogencarbonates such as sodium hydrogen carbonate and potassium hydrogencarbonate; metal hydrides such as lithium hydride, sodium hydride andpotassium hydride; ammonia; and the like. The organic base includes, forexample, alkali metal salts or alkaline earth metal salts such aslithium methoxide, lithium ethoxide, lithium tert-butoxide, sodiummethoxide, sodium ethoxide, sodium tert-butoxide, potassium methoxide,potassium ethoxide, potassium tert-butoxide, potassium naphthalenide,sodium acetate, potassiumacetate, magnesiumacetate, calciumacetate,lithium diethylamide, lithium diisopropylamide, lithiumbis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide, potassiumbis(trimethylsilyl)amide, lithium diphenylphosphide, sodiumdiphenylphosphide and potassium diphenylphosphide; organic amines suchas triethylamine, diisopropylethylamine, N,N-dimethylaniline,piperidine, pyridine, 4-dimethylaminopyridine,1,5-diazabicyclo[4.3.0]non-5-ene, 1,8-diazabicyclo[5.4.0]undec-7-ene,tri-n-butylamine and N-methylmorpholine; organometallic compounds suchas methyl lithium, ethyl lithium, n-propyl lithium, isopropyl lithium,n-butyl lithium, s-butyl lithium, tert-butyl lithium, phenyl lithium,methyl magnesium chloride, ethyl magnesium chloride, n-propyl magnesiumchloride, isopropyl magnesium chloride, n-butyl magnesium chloride,s-butyl magnesium chloride, tert-butyl magnesium chloride, phenylmagnesium chloride, methyl magnesium bromide, ethyl magnesium bromide,n-propyl magnesium bromide, isopropyl magnesium bromide, n-butylmagnesium bromide, s-butyl magnesium bromide, tert-butyl magnesiumbromide and phenyl magnesium bromide; optically active forms (opticallyactive diamine compounds) of the diamine compounds illustrated above asthe chiral ligands and racemic compounds thereof; and the like.

The amount of the base used is suitably selected usually in the range of0 to 100 equivalents, preferably 0 to 10 equivalents, relative to theunsaturated compound.

The quaternary ammonium salt as the additive includes, for example, aquaternary ammonium salt having 4 to 24 carbon atoms. Specific examplesof the quaternary ammonium salt include tetrabutyl ammonium fluoride,tetrabutyl ammonium chloride, tetrabutyl ammonium bromide, tetrabutylammonium iodide, triethyl benzyl ammonium chloride, tetrabutyl ammoniumtriphenyl difluorosilicate and the like.

The amount of the quaternary ammonium salt used is suitably selectedusually in the range of 0.0001 to 100 equivalents, preferably 0.001 to10 equivalents, relative to the unsaturated compound.

The quaternary phosphonium salt includes, for example, C4 to C36quaternary phosphonium salts. Specific examples of the quaternaryphosphonium salt include tetraphenyl phosphonium chloride, tetraphenylphosphonium bromide, tetraphenyl phosphonium iodide, methyl triphenylphosphonium chloride, methyl triphenyl phosphonium bromide, methyltriphenyl phosphonium iodide and the like.

The amount of the quaternary phosphonium salt used is suitably selectedusually in the range of 0.0001 to 100 equivalents, preferably 0.001 to10 equivalents, relative to the unsaturated compound.

The phosphorus compound may be the same as the phosphorus compoundrepresented by the above-mentioned formula (P).

Specific examples of the phosphorus compound include phosphine compoundssuch as triphenylphosphine, tritolylphosphine, trimethylphosphine,triethylphosphine, methyl diphenylphosphine, dimethyl phenylphosphine,diphenyl phosphinomethane (dppm), diphenyl phosphinoethane (dppe),diphenyl phosphinopropane (dppp), diphenyl phosphinobutane (dppb) anddiphenyl phosphinoferrocene (dppf), and phosphite compounds such astrimethyl phosphite, triethyl phosphite, triphenyl phosphite and thelike.

The amount of the phosphorus compound used is suitably selected usuallyin the range of 0.00001 to 1 equivalent, preferably 0.0001 to 1equivalent, relative to the unsaturated compound.

The halogen includes bromine, iodine and the like.

The amount of the halogen used is suitably selected usually in the rangeof 0.0001 to 100 equivalents, preferably 0.001 to 10 equivalents,relative to the unsaturated compound.

The reducing agent includes, for example, sodium borohydride, lithiumaluminum hydride, diisobutylaluminum hydride and the like.

The amount of the reducing agent used is suitably selected usually inthe range of 0.00001 to 1 equivalent, preferably 0.0001 to 1 equivalent,relative to the unsaturated compound.

These additives may be used alone or in a suitable combination of two ormore thereof.

The hydrogenated compound of the unsaturated compound, obtained by theproduction method of the present invention, is a compound obtained bycarrying out homogeneous hydrogenation of said unsaturated compound, andpreferably an optically active compound thereof is obtained. That is, inthe present invention, the homogeneous hydrogenation is preferably ahomogeneous asymmetric hydrogenation. Accordingly, the hydrogenatedcompound of the unsaturated compound obtained in the present inventionis preferably an optically active compound, and an optically activecompound corresponding to each unsaturated compound is obtained. Forexample, the compound obtained by hydrogenation of the alkene is anoptically active alkane; the compound obtained by asymmetrichydrogenation of the ketone is an optically active alcohol; the compoundobtained by hydrogenation of the imine is an optically active amine; thecompound obtained by hydrogenation of the ketocarboxylic acid is anoptically active hydroxyester; and the compound obtained byhydrogenation of the ketoalkene is a hydroxyalkene, a hydroxyalkaneand/or a ketoalkane, respectively.

The optically active alkane obtained by asymmetric hydrogenation of thealkene includes, for example, an optically active alkane represented bythe following formula (31):

The optically active alcohol obtained by asymmetric hydrogenation of theketone includes, for example, an optically active alcohol represented bythe following formula (32):

The optically active amine obtained by asymmetric hydrogenation of theimine includes, for example, an optically active amine represented bythe following formula (33):

The optically active hydroxyester obtained by asymmetric hydrogenationof the ketocarboxylic acid includes, for example, an optically activehydroxyester represented by the following formula (34):

The optically active hydroxyalkene, the optically active hydroxyalkaneand the optically active ketoalkane obtained by asymmetric hydrogenationof the ketoalkene are, for example, represented by the followingformulae (35) to (37), respectively:

In the above formulae, the symbol * represents an asymmetric carbonatom; and R³¹ to R⁴⁵, Q¹¹ and Q¹² are the same as described above.Provided that, the symbol * may not be an asymmetric carbon atomdepending on the kind of R³¹ to R⁴⁵ in the cases where R³⁵ is equal toR³⁶, or either R³⁵ or R³⁶ is a hydrogen atom in the formula (32) and thelike.

Specific examples of the optically active compounds include opticallyactive forms of the hydrogenated compounds of unsaturated compounds asexemplified by the above-mentioned hydrogenated compounds of unsaturatedcompounds as specific examples.

The resulting optically active compound may be subjected as necessary topost-treatment such as purification, isolation and the like, or toprotection of functional group(s) and the like, followed bypost-treatment such as purification, isolation and the like. Specificmethods of post-treatment are the same methods as described above.

The catalyst for homogeneous hydrogenation of the present invention isnot only obtained at a low price, but also improved workability becausehandled easily. The process for producing an optically active compound,using this catalyst for homogenous hydrogenation as the catalyst forhomogenous asymmetric hydrogenation, becomes more able to control theasymmetric hydrogenation of an unsaturated compound, is able to give anintentional optically active compound, and is able to give a desiredoptically active compound that is a hydrogenated compound of anunsaturated compound with a high yield and a high optical purity, bychanging the kind of the chiral ligand used.

Hydrogenated compounds of unsaturated compounds, particularly opticallyactive compounds of the hydrogenated compounds, obtained according tothe production process of the present invention are useful asintermediates of medicines and agrochemicals, perfumes and the like.

EXAMPLES

Hereinafter, the present invention will be described in more detail byway of the Examples, but the present invention is not limited thereto.

In the following Examples, instruments used for measurements of physicalproperties etc. are as follows:

-   NMR: DRX-500 manufactured by Bruker-   Gas chromatography (GC): 5890-II manufactured by Hewlett Packard-   Mass spectrometry: ESI-MS (LCMS-IT-TOF manufactured by Shimadzu    Corporation), EI-MS (Poralis Q manufactured by Thermo Electron)

In the Examples below, the symbol “n” represents a natural number.

Example 1

Synthesis of [CuBr((S)-SEGPHOS)]_(n)

Into a reaction vessal was put 500 mg (0.819 mmol) of (S)-SEGPHOS and176 mg (1.23 mmol, 1.5 equivalents) of copper(I) bromide (CuBr),followed by replacing with nitrogen in the vessal, and then 5 mL oftoluene was added. The reaction was carried out with stirring at roomtemperature for 16 hours. The reaction solution was purified by columnchromatography on silica gel, and then the solvent was distilled away,to give the title compound.

³¹P-NMR (CDCl₃): δ; −8.1

Example 2

Synthesis of [CuCl((S)-SEGPHOS)]_(n)

Into a reaction vessal was put 1.0 g (1.64 mmol) of (S)-SEGPHOS and 2.44mg (2.46 mmol, 1.5 equivalents) of copper (I) chloride (CuCl), followedby replacing with nitrogen in the vessal, and then 5 mL of toluene wasadded. The reaction was carried out with stirring at room temperaturefor 16 hours. The reaction solution was purified by columnchromatography on silica gel, and then the solvent was distilled away,to give the title compound.

³¹P-NMR (CDCl₃): δ; −7.0

Example 3

Synthesis of [CuI((S)-SEGPHOS)]_(n)

Into a reaction vessal was put 500 mg (0.819 mmol) of (S)-SEGPHOS and234 mg (1.23 mmol, 1.5 equivalents) of copper(I) iodide (CuCl), followedby replacing with nitrogen in the vessal, and then 5 mL of toluene wasadded. The reaction was carried out with stirring at room temperaturefor 16 hours. The reaction solution was purified by columnchromatography on silica gel, and then the solvent was distilled away,to give the title compound.

³¹P-NMR (CDCl₃): δ; −9.2

Example 4

Synthesis of [Cu(OTf)((S)-SEGPHOS)]_(n)

Into a reaction vessal was put 500 mg (0.819 mmol) of (S)-SEGPHOS and309 mg (1.23 mmol, 1.5 equivalents) of CuOTf.0.5C₆H₆, followed byreplacing with nitrogen in the vessal, and then 5 mL of toluene wasadded. The reaction was carried out with stirring at room temperaturefor 16 hours. The reaction solution was filtered through Celite, andthen the solvent was distilled away, to give the title compound.

³¹P-NMR (CDCl₃): δ; −1.1

¹⁹F-NMR (CDCl₃): δ; −77.4

Examples 5 to 8

Homogeneous Asymmetric Hydrogenation of Isophorone 1 Using Cu(I) Salt,Shown in the Following Scheme A

Into a 100-mL stainless-steel autoclave was put 0.03 mmol of the coppersalt (CuX) shown in Table 1 below, 18.3 mg (0.03 mmol) of (S)-SEGPHOSand 28.8 mg (0.30 mmol) of sodium tert-butoxide (NaO-t-Bu), followed byreplacing with nitrogen in the autoclave, and then 2 mL of a mixedsolvent of toluene and tert-butyl alcohol (t-BuOH) by a ratio of 3:1,and isophorone 1 (0.15 mL, 1.0 mmol) were added. The reaction wascarried out with stirring under a hydrogen pressure of 3.0 MPa at 50° C.for 16 to 17 hours. The reaction mixture was analyzed by using GC. Theresults are shown in Table 1.

TABLE 1 Yield (%) [Optical Purity (% ee)] Reaction 3,3,5- 3,3,5-3,3,5-Trimethyl- Example CuX Time (h) Trimethylcyclohexanone 2Trimethylcyclohexanol 3 2-cyclohexenol 4 5 CuCl 16 21[94] 6 trace 6 CuBr17 28[93] 15 trace 7 CuI 17 12[88] 1 trace 8 CuOTf^(c)) 17 26[93]11[96]^(b)) trace (91/9)^(a)) ^(a))dr (Diastereomer ratio) ^(b))Opticalpurity (% ee) of main diastereomer ^(c))Cu(OTf)•0.5C₆H₆

Examples 9 to 11

Homogeneous Asymmetric Hydrogenation Using Cu(II) Salt Shown in theAbove Scheme A

Into a 100-mL stainless-steel autoclave was put 0.03 mmol of the coppersalt (CuX₂) shown in Table 2 below, 18.3 mg (0.03 mmol) of (S)-SEGPHOSand 28.8 mg (0.30 mmol) of NaO-t-Bu, followed by replacing with nitrogenin the autoclave, and then 2 mL of a mixed solvent of toluene and t-BuOHby a ratio of 3:1, and isophorone 1 (0.15 mL, 1.0 mmol) were added. Thereaction was carried out with stirring under a hydrogen pressure of 5.0MPa at 50° C. for 15 to 17 hours. The reaction mixture was analyzed byusing GC. The results are shown in Table 2.

TABLE 2 Yield (%) [Optical Purity (% ee)] Reaction 3,3,5- 3,3,5-3,3,5-Trimethyl- Example CuX₂ Time (h) Trimethylcyclohexanone 2Trimethylcyclohexanol 3 2-cyclohexenol 4 9 CuCl₂ 17 28[94] 22[96]^(b))trace (93/7)^(a)) 10 Cu(NO₃)₂ 15 20[95] 3 trace 11 Cu(OTf)₂ 17 19[95] 4trace ^(a))dr (Diastereomer ratio) ^(b))Optical purity (% ee) of maindiastereomer

Examples 12 to 16

Homogeneous Asymmetric Hydrogenation of Isophorone 1 Using[CuX((S)-SEGPHOS)]_(n) Represented by the Above Scheme A, Shown in theAbove Scheme A

Into a 100-mL stainless-steel autoclave was put 0.03 mmol (Cu reduced)of the chiral copper complex [CuX((S)-SEGPHOS)]_(n) obtained in each ofExamples 1 to 4 and 28.8 mg (0.30 mmol) of NaO-t-Bu, followed byreplacing with nitrogen in the autoclave, and then 2 mL of a mixedsolvent of toluene and t-BuOH in a ratio of 3:1, and isophorone 1 (0.15mL, 1.0 mmol) were added. The reaction was carried out with stirringunder a hydrogen pressure of 5.0 MPa at 50° C. The reaction mixture wasanalyzed by using GC. The results are shown in Table 3.

TABLE 3 Yield (%) [Optical Purity (% ee)] Reaction 3,3,5- 3,3,5-3,3,5-Trimethyl-2- Example X Time (h) Trimethylcyclohexanone 2Trimethylcyclohexanol 3 cyclohexenol 4 12 Cl 17 28[90] 37[92]^(b)) trace(92/8)^(a)) 13 Br 17 27[90] 43[92]^(b)) trace (93/7)^(a)) 14 Br 4813[91] 78[92]^(b)) trace (92/8)^(a)) 15 I 18 18[75] 3 trace 16 OTf 1721[93] 6 trace ^(a))dr (Diastereomer ratio) ^(b))Optical purity (% ee)of main diastereomer

Example 17

Homogeneous Asymmetric Hydrogenation of Isophorone 1 Using[CuBr((S)-SEGPHOS)]_(n) Shown in the Above Scheme A

Into a 100-mL stainless-steel autoclave was put 22.6 mmol (0.03 mmol; Cureduced) of the chiral copper complex [CuBr ((S)-SEGPHOS)]_(n) obtainedin the same manner as described in Example 1, 18.3 mg (0.03 mmol) of(S)-SEGPHOS and 28.8 mg (0.30 mmol) of NaO-t-Bu, followed by replacingwith nitrogen in the autoclave, and then 2 mL of a mixed solvent oftoluene and t-BuOH in a ratio of 3:1, and isophorone 1 (0.15 mL, 1 mmol)were added. The reaction was carried out with stirring under a hydrogenpressure of 5.0 MPa at 50° C. for 17 hours. The reaction mixture wasanalyzed by using GC. The results indicated that the products shown inthe scheme A, that is, 3,3,5-trimethylcyclohexanone 2 was obtained in ayield of 18% (optical purity 93% ee), 3,3,5-trimethylcyclohexanol 3 wasobtained in a yield of 61% (dr: 93/7, optical purity of maindiastereomer: 95% ee), and 3,3,5-trimethyl-2-cyclohexenol 4 was obtainedin a trace amount, respectively.

Examples 18 and 19

Homogeneous Asymmetric Hydrogenation of Isophorone 1 UsingCuF(PPh₃)₃.2EtOH Represented by the Above Scheme A, Shown in the AboveScheme A

Into a 100-mL stainless-steel autoclave was put 28.8 mg (0.03 mmol) ofCuF(PPh₃)₃.2EtOH, 0.03 mmol of chiral ligand and 28.8 mg (0.30 mmol) ofNaO-t-Bu, followed by replacing with nitrogen in the autoclave, and then2 ml of isopropyl alcohol (IPA) and isophorone 1 (0.45 mL, 3.0 mmol)were added. The reaction was carried out with stirring under a hydrogenpressure of 5.0 MPa at 30° C. for 16 hours. The reaction mixture wasanalyzed by using GC. The results are shown in Table 4.

TABLE 4 Yield (%) [Optical Purity (% ee)] 3,3,5- 3,3,5- 3,3,5- ExampleChral Ligand Trimethylcyclohexanone 2 Trimethylcyclohexanol 3Trimethyl-2-cyclohexenol 4 18 (R,R)-SKEWPHOS trace  9[24]^(b))  83[11]19 (S)-SEGPHOS trace 14[81]^(b)) 10[6] ^(b))Optical purity (% ee) ofmain diastereomer

Example 20

Homogeneous Asymmetric Hydrogenation of Acetophenone Using[CuBr((S)-SEGPHOS)]_(n)

Into a 20-ml Schrenck tube was put 21.3 mg (0.029 mmol (Cu reduced)) of[CuBr((S)-SEGPHOS)]_(n) obtained in the same manner as described inExample 1 and 27.8 mg (0.29 mmol) of NaO-t-Bu, followed by replacingwith nitrogen in the Schrenck tube, and then 1.4 mL of toluene wasadded. The reaction was carried out with stirring at room temperaturefor 1 hour. And then, a separate 100-mL stainless-steel autoclave wasset, followed by replacing with nitrogen in the autoclave. Into thisautoclave was put 113 μL (0.96 mmol) of acetophenone and 450 μL oft-BuOH, and then the previously prepared content of the Schrenck tubewas added to the autoclave. The reaction was carried out with stirringunder a hydrogen pressure of 3 MPa at 50° C. for 19 hours. The reactionmixture was analyzed by using GC. The results indicated that 1-phenethylalcohol, which is a hydrogenated compound of acetophenone, was obtainedin a yield of 65.4% and an optical purity of 65.7% ee.

Example 21

Homogeneous Asymmetric Hydrogenation of 2-Acetylfuran Using[CuBr((S)-SEGPHOS)]_(n)

Into a 100-mL stainless-steel autoclave was put 22.6 mg [0.03 mmol (Cureduced)] of [CuBr((S)-SEGPHOS)]_(n) obtained in the same manner asdescribed in Example 1 and 28.8 mg (0.30 mmol) of NaO-t-Bu, followed byreplacing with nitrogen in the autoclave, and then 1.5 mL of toluene,500 μL of t-BuOH and 110.1 mg (1.0 mmol) of 2-acetylfuran were added.The reaction was carried out with stirring under a hydrogen pressure of3.0 MPa at 50° C. for 17 hours. The reaction mixture was analyzed byusing GC. The results indicated that 1-(2-furyl)ethanol, which is ahydrogenated compound of 2-acetylfuran, was obtained in a yield of 13%and an optical purity of 59.5% ee.

Example 22

Homogeneous Asymmetric Hydrogenation of Isophorone Using [CuH(PPh₃)]₆

Into a 100-mL stainless-steel autoclave was put 9.8 mg [0.03 mmol (Cureduced)] of [CuH(PPh₃)]₆ and 18.3 mg (0.03 mmol) of (S)-SEGPHOS,followed by replacing with nitrogen in the autoclave, and then 2 ml of amixed solvent of toluene and t-BuOH in a ratio of 3:1, and 0.15 mL (1.0mmol) of isophorone, were added. The reaction was carried out withstirring under a hydrogen pressure of 5.0 MPa at 50° C. for 17 hours.The reaction mixture was analyzed by using GC. The results are shown inTable 5.

Example 23

Homogeneous Asymmetric Hydrogenation of Isophorone Using [CuH(PPh₃)]₆

In Example 22, the reaction was carried out in the same manner asdescribed in Example 22 except for adding 28.8 mg (0.30 mmol) ofNaO-t-Bu as a base thereto and changing the reaction time to 18 hours.The reaction mixture was analyzed by using GC. The results are alsoshown in Table 5.

TABLE 5 Yield (%) [Optical Purity (% ee)] 3,3,5-Trimethyl-3,3,5-Trimethyl- Example Base cyclohexanone 2 cyclohexanol 3 22 absent 8[55] 1 23 present 15[73] 3

Example 24

Production of Methyl 2-methylbutanoate

Into a 100-mL stainless-steel autoclave was put 114 mg (1 mmol) ofmethyl tiglate, 22.6 mg [0.03 mmol (Cu reduced)] of[CuBr((S)-SEGPHOS)]_(n) and 33.6 mg (0.3 mmol) of potassiumtert-butoxide (^(t)BuOK), followed by replacing with nitrogen in theautoclave, and then 1.1 mL of a mixed solvent of toluene and t-BuOH in aratio of 3:1 was added. The reaction was carried out with stirring undera hydrogen pressure of 3.0 MPa at 85° C. for 17 hours to give methyl2-methylbutanoate, which is a hydrogenated compound of methyl tiglate,in a yield of 63.8%.

Example 25

Production of Methyl 2-methyl 3-phenylpropionate

Into a 100-mL stainless-steel autoclave was put 176 mg (1 mmol) ofmethyl 2-methyl-3-phenylpropenate, 22.6 mg (0.03 mmol (equivalent inCu)) of [CuBr((S)-SEGPHOS)]_(n) and 33.6 mg (0.3 mmol) of ^(t)BuOK wereintroduced in to a 100-mL stainless-steel autoclave, followed byreplacing with nitrogen in the autoclave, and then 1.8 mL of a mixedsolvent of toluene and t-BuOH in a ratio of 3:1 was added. The reactionwas carried out with stirring under a hydrogen pressure of 3.0 MPa at85° C. for 17 hours to give methyl 2-methyl 3-phenylpropionate, which isa hydrogenated compound of methyl 2-methyl-3-phenylpropenate, in a yieldof 54.7%.

Example 26

Production of Methyl 2-acetamidopropionate

Into a 100-mL stainless-steel autoclave was put 143 mg (1 mmol) ofmethyl 2-acetamido-2-propenate, 22.6 mg [0.03 mmol (Cu reduced)] of[CuBr((S)-SEGPHOS)]_(n) and 33.6 mg (0.3 mmol) of ^(t)BuOK, followed byreplacing with nitrogen in the autoclave, and then 1.4 mL of a mixedsolvent of toluene and t-BuOH in a ratio of 3:1 was added. The reactionwas carried out with stirring under a hydrogen pressure of 3.0 MPa at85° C. for 17 hours to give methyl 2-acetamidopropionate, which is ahydrogenated compound of methyl 2-acetamido-2-propenate in a yield of52.5%.

Example 27

Synthesis of [CuCl((R,R)-SKEWPHOS)(PPh₃)]_(n)

Into a 20-ml Schrenck tube was put 131 mg (0.5 mmol) of triphenylphosphine was introduced into a 20-ml Schrenck tube previously flushedwith nitrogen, and then 1 mL of toluene was added to it to form ahomogeneous solution. 49.5 mg (0.5 mmol) of CuCl and 5 mL of toluenewere added to the solution and stirred at room temperature for 3 hours.Then, 220 mg (0.5 mmol) of (R,R)-SKEWPHOS was added thereto and stirredfor 30 minutes, and then 2.5 mL of toluene was further added, and themixture was stirred at room temperature for 3 hours. The resulting whitesuspension was filtered and solids were washed with toluene, whereby 320mg of the objective title compound (yield 80%) was obtained as a whitesolid.

³¹P-NMR (CDCl₃): δ; −10.0 (br, 1P), 2.3 (br, 2P)

EI-MS: 765.3[(M-Cl)+]

ESI-MS: 765.2[(M-Cl)+]

Examples 28 to 30

Homogeneous Asymmetric Hydrogenation of Acetophenone Using [CuCl((R,R)-SKEWPHOS) (PPh₃)]_(n)

Into a 100-mL stainless-steel autoclave was put 24.0 mg (0.03 mmol) of[CuCl((R,R)-SKEWPHOS) (PPh₃)]_(n) obtained in Example 27, triphenylphosphine of the amount shown in Table 6 below, and 28.8 mg (0.30 mmol)of NaO-t-Bu, followed by replacing with nitrogen in the autoclave, andthen 2.0 mL of isopropyl alcohol and 1.05 mL (9.0 mmol) of acetophenonewere added. The reaction was carried out with stirring under a hydrogenpressure of 5 MPa at 30° C. for 16 to 17 hours to give 1-phenethylalcohol which is a hydrogenated compound of acetophenone. The reactionmixture was analyzed by using GC. The results are shown in Table 6.

TABLE 6 Amount (equivalent) of 1-Phenethyl alcohol triphenylphosphineused Optical relative to 1 equivalent Yield Purity Example of Cu (%) (%ee) 28 0 55 44 29 1 94 47 30 2 97 47

Examples 31 to 40

Homogeneous Asymmetric Hydrogenation of Acetophenone (Addition of aBase)

Into a 100-mL stainless-steel autoclave was put a copper compound [0.03mmol (Cu reduced)], 13.2 mg (0.03 mmol) of (R,R)-SKEWPHOS and 28.8 mg(0.30 mmol) of NaO-t-Bu, followed by replacing with nitrogen in theautoclave, and then 2.0 mL of solvent and 1.05 mL (9.0 mmol) ofacetophenone were added thereto. The reaction was carried out withstirring under a prescribed hydrogen pressure at a prescribedtemperature for 16 to 17 hours. Table 7 shows the copper compound, thesolvent, the hydrogen pressure and the reaction temperature used in thereaction, and the yield and optical purity of 1-phenethylalcohol whichis a hydrogenated compound of acetophenone, as analyzed by using GC ofthe reaction mixture.

TABLE 7 Hydrogen Optical Pressure Temperature Yield Purity ExampleCopper Compound Solvent (MPa) (° C.) (%) (% ee) 31[CuCl(R,R)•SKEWPHOS]_(n) t-BuOH 3.0 50 >99 46 32 CuF(PPh₃)₃•2EtOH t-BuOH3.0 30 >99 53 33 CuF(PPh₃)₃•2EtOH EtOH 5.0 30 >99 41 34 CuF(PPh₃)₃•2EtOHIPA 3.0 30 >99 47 35 CuF(PPh₃)₃•2EtOH t-Bu(Me)CHOH 5.0 30 >99 56 36CuF(PPh₃)₃•2EtOH (R)-t-Bu(Me)CHOH 5.0 30 >99 55 37 CuF(PPh₃)₃•2EtOH CPME5.0 30 >99 55 38 CuCl(PPh₃)₃ IPA 3.0 30 >99 47 39 CuCl(P(m-tol)₃)₃ CPME5.0 30 94 62 40 Cu(NO₃)(PPh₃)₂ IPA 5.0 50 >99 43 t-BuOH: tert-butylalcohol EtOH: ethyl alcohol IPA: isopropyl alcohol t-Bu(Me)CHOH:3,3-dimethylbutan-2-ol (R)-t-Bu(Me)CHOH: (R)-3,3-dimethylbutan-2-olCPME: cyclopentyl methyl ether tol: —C₆H₄CH₃

Examples 41 to 46

Homogeneous Asymmetric Hydrogenation of Acetophenone

Into a 100-mL stainless-steel autoclave was put 0.03 mmol of the copperhalide (CuX), triphenyl phosphine (PPh₃), and (R,R)-SKEWPHOS shown inTable 8 below, respectively, and 28.8 mg (0.30 mmol) of NaO-t-Bu,followed by replacing with nitrogen in the autoclave, and then 2.0 mL ofIPA and 1.05 mL (9.0 mmol) of acetophenone were added thereto. Thereaction was carried out with stirring under a hydrogen pressure of 5.0MPa at 30° C. for 16 to 17 hours. Table 8 shows the copper halide (CuX)used, the amount of (R,R)-SKEWPHOS used, the amount of triphenylphosphine used, and the yield and optical purity of 1-phenethyl alcoholwhich is a hydrogenated compound of acetophenone, as analyzed by usingGC analysis of the reaction mixture.

TABLE 8 Used amount Used amount (equivalent) of (equivalent) oftriphenyl Optical (R,R)-SKEWPHOS phosphine Yield Purity Example CuXrelative to CuX relative to CuX (%) (% ee) 41 CuI 1 1 7 31 42 CuBr 1 112 43 43 CuCl 1 1 50 46 44 CuCl 1 2 >99 47 45 CuCl 1 3 >99 47 46 CuCl 20 53 45

Examples 47 to 60

Homogeneous Asymmetric Hydrogenation of Acetophenone

Into a 100-mL stainless-steel autoclave was put 3.0 mg (0.03 mmol) ofCuCl, 0.09 mmol of ligand, 13.2 mg (0.03 mmol) of (R,R)-SKEWPHOS and28.8 mg (0.30 mmol) of NaO-t-Bu, followed by replacing with nitrogen inthe autoclave, and then 2.0 mL of IPA and 1.05 mL (9.0 mmol) ofacetophenone were added thereto. The reaction was carried out withstirring under a hydrogen pressure of 5.0 MPa at 30° C. for 16 to 17hours. Table 9 shows the ligand used, and the yield and optical purityof 1-phenethyl alcohol which is a hydrogenated compound of acetophenone,as analyzed by using GC of the reaction mixture.

TABLE 9 Optical Yield Purity Example Ligand (%) (% ee) 47 PCy₃ 25 35 48P(t-Bu)₃ 16 47 49 P(OPh)₃ 3 37 50 P(2-furyl)₃ 7 47 51 P(C₆F₅)₃ 7 38 52PPh₂(2-naphthyl) >99 50 53 P(1-naphtyl)₃ 32 20 54 P(2-naphthy)₃ 80 50 55P(o-tolyl)₃ 29 40 56 P(m-tolyl)₃ 97 53 57 P(p-tolyl)₃ >99 50 58P(4-t-Bu-C₆H₄)₃ 58 46 59 P(3,5-xylyl)₃ >99 57 60 P(3,5-di-t-Bu-C₆H₃)₃ 3434

Examples 61 and 62

Homogeneous Asymmetric Hydrogenation of Acetophenone (Addition 5 of aBase)

Into a 100-mL stainless-steel autoclave was put 28.8 mg [0.03 mmol/Cu(Cu reduced)] of CuF(PPh₃)₃.2EtOH, 39.6 mg (0.09 mmol) of (R,R)-SKEWPHOSand 28.8 mg (0.30 mmol) of NaO-t-Bu, followed by replacing with nitrogenin the autoclave, and then 7.0 mL of solvent and 3.5 mL (30 mmol) ofacetophenone were added thereto. The reaction was carried out withstirring under a hydrogen pressure of 5.0 MPa at 50° C. for 24 hours.Table 10 shows the solvent used, and the yield and optical purity of1-phenethyl alcohol which is a hydrogenated compound of acetophenone, asanalyzed by using GC of the reaction mixture.

TABLE 10 Optical Yield Purity Example Solvent (%) (% ee) 61 IPA >99 4362 t-BuOH >99 48

Example 63

Homogeneous Asymmetric Hydrogenation of Acetophenone (Silylenol EtherAddition)

Into a 100-mL stainless-steel autoclave was put 28.8 mg (0.03 mmol/Cu)of CuF(PPh₃)₃.2EtOH, 13.2 mg (0.03 mmol) of (R,R)-SKEWPHOS and 61.5 μL(0.30 mmol) of 1-phenyl-1-(trimethylsiloxy)ethylene, followed byreplacing with nitrogen in the autoclave, and then 2.0 mL of t-BuOH and1.05 mL (9.0 mmol) of acetophenone were added thereto. The reaction wascarried out with stirring under a hydrogen pressure of 3.0 MPa at 50° C.for 16 hours. The reaction mixture was analyzed by using GC. The resultsrevealed that 1-phenethyl alcohol, which is a hydrogenated compound ofacetophenone, was obtained in a yield of 24% and in an optical purity of50% ee.

Examples 64 and 65

Homogeneous Asymmetric Hydrogenation of Acetophenone Using [CuH(PPh₃)]₆

Into a 100-mL stainless-steel autoclave was put 9.8 mg (0.03 mmol(equivalent in Cu)) of [CuH(PPh₃)]₆, 13.2 mg (0.03 mmol) of(R,R)-SKEWPHOS and 28.8 mg (0.30 mmol) of NaO-t-Bu, followed byreplacing with nitrogen in the autoclave, and then 2.0 mL of solvent and1.05 mL (9.0 mmol) of acetophenone were added thereto. The reaction wascarried out with stirring under a hydrogen pressure of 3.0 MPa at 30° C.for 16 hours. Table 11 shows the solvent used, and the yield and opticalpurity of 1-phenethyl alcohol which is a hydrogenated compound ofacetophenone, as analyzed by using GC of the reaction mixture.

TABLE 11 Optical Yield Purity Example Solvent (%) (% ee) 64 IPA >99 4965 toluene 79 56

Examples 66 to 68

Homogeneous Asymmetric Hydrogenation of Substituted Acetophenone

Into a 100-mL stainless-steel autoclave was put 28.8 mg (0.03 mmol) ofCuF(PPh₃)₃.2EtOH, 13.2 mg (0.03 mmol) of (R,R)-SKEWPHOS and 28.8 mg(0.30 mmol) of NaO-t-Bu, followed by replacing with nitrogen in theautoclave, and then 2.0 mL of IPA and 9.0 mmol of substitutedacetophenone were added thereto. The reaction was carried out withstirring under a hydrogen pressure of 5.0 MPa at 30° C. for 16 hours.Table 12 shows the substituted acetophenone used, and the yield andoptical purity of a hydrogenated compound of substituted acetophenone,as analyzed by using GC of the reaction mixture.

TABLE 12 Optical Yield Purity Example Substituted Acetophenone (%) (%ee) 66 4′-Bromoasetophenone >99 48 67 2′-mrthylacetophenone 89 60 683′,5′-bis(trifluoromethyl)acetophenone >99 5

Examples 69 to 79

Homogeneous Asymmetric Hydrogenation of Substituted Acetophenone

Into a 100-mL stainless-steel autoclave was put 3.0 mg (0.03 mmol) ofCuCl, 31.1 mg (0.09 mmol) of tris(3,5-dimethylphenyl)phosphine, 13.2 mg(0.03 mmol) of (R,R)-SKEWPHOS and 28.8 mg (0.30 mmol) of NaO-t-Bu,followed by replacing with nitrogen in the autoclave, and then 2.0 mL ofIPA and 1.05 mL (9.0 mmol) of substituted acetophenone were addedthereto. The reaction was carried out with stirring under a hydrogenpressure of 5 MPa at 30° C. for 16 to 17 hours. Table 13 shows thesubstituted acetophenone used, and the yield and optical purity of ahydrogenated compound of substituted acetophenone, as analyzed by usingGC of the reaction mixture.

TABLE 13 Optical Yield Purity Example Substituted Acetophenone (%) (%ee) 69 2′-Methylacetophenone 87 86 70 (Note 1) 2′-Methylacetophenone 9586 71 (Note 2) 2′-Methylacetophenone 23 90 72 2′-Bromoacetophenone 19 7473 2′-Trifluoromethylacetophenone 47 89 74 2′-Methoxyacetophenone 58 8475 2′-Aminoacetophenone 26 83 76 1-Acetonaphthone 82 64 773′-Methylacetophenone >99 63 78 3′-Bromoacetophenone 48 44 794′-Methylacetophenone 93 57 Note 1: 0.25 mmol oftris(3,5-dimethylphenyl)phosphine was used. Note 2:2,4-dimethyl-3-pentanol was used as solvent.

Examples 80

Homogeneous Asymmetric Hydrogenation of Pinacolin

Into a 100-mL stainless-steel autoclave was put 28.8 mg (0.03 mmol(equivalent in Cu)) of CuF(PPh₃) 32EtOH, 13.2 mg (0.03 mmol) of(R,R)-SKEWPHOS and 28.8 mg (0.30 mmol) of NaO-t-Bu, followed byreplacing with nitrogen in the autoclave, and then 2.0 mL of IPA and1.13 mL (9.0 mmol) of pinacolin were added thereto. The reaction wascarried out with stirring under a hydrogen pressure of 5.0 MPa at 30° C.for 16 hours. The reaction mixture was analyzed by using GC. The resultsrevealed that 3,3-dimethylbutan-2-ol, which is a hydrogenated compoundof pinacolin, was obtained in a yield of 79% and in an optical purity of17% ee.

Examples 81

Homogeneous Asymmetric Hydrogenation of 2-acetylfuran

Into a 100-mL stainless-steel autoclave was put 28.8 mg (0.03 mmol(equivalent in Cu)) of CuF(PPh₃)₃.2EtOH, 13.2 mg (0.03 mmol) of(R,R)-SKEWPHOS and 28.8 mg (0.30 mmol) of NaO-t-Bu, followed byreplacing with nitrogen in the autoclave, and then 2.0 mL of IPA and0.90 mL (9.0 mmol) of 2-acetylfuran were added thereto. The reaction wascarried out with stirring under a hydrogen pressure of 5.0 MPa at 30° C.for 16 hours. The reaction mixture was analyzed by using GC. The resultsindicated that 1-(2-furyl)ethanol, which is a hydrogenated compound of2-acetylfuran, was obtained in a yield of 99% and in an optical purityof 31% ee.

Examples 82

Homogeneous Asymmetric Hydrogenation of 2,3,3-trimethylindolenine

Into a 100-mL stainless-steel autoclave was put 26.5 mg (0.03 mmol) ofCuCl(PPh₃)₃, 13.2 mg (0.03 mmol) of (R,R)-SKEWPHOS and 28.8 mg (0.30mmol) of NaO-t-Bu, followed by replacing with nitrogen in the autoclave,and then 2.0 mL of IPA and 161 μL (1.0 mmol) of2,3,3-trimethylindolenine were added thereto. The reaction was carriedout with stirring under a hydrogen pressure of 5.0 MPa at 30° C. for 16hours. The reaction mixture was analyzed by using GC. The resultsrevealed that 2,3,3-trimethyl-2,3-dihydro-1H-indole, which is ahydrogenated compound of 2,3,3-trimethylindolene, was obtained in ayield of 7% and in an optical purity of 57% ee.

Examples 83 to 96

Homogeneous Asymmetric Hydrogenation of Acetophenone

Into a 100-mL stainless-steel autoclave was put 11.7 mg (0.018 mmol(equivalent in Cu)) of Cu(NO₃)₂(PPh₃)₂ and a chiral ligand (0.018 mmol),followed by replacing with nitrogen in the autoclave, and then 2.0 mL(0.18 mmol) of 0.09 M NaO-t-Bu IPA solution and 1.05 mL (9.0 mmol) ofacetophenone were added thereto. The reaction was carried out withstirring under a hydrogen pressure of 5.0 MPa at 30° C. for 16 to 17hours. The reaction mixture was analyzed by using GC. Table 14 shows thechiral ligand used, and the yield and optical purity of 1-phenethylalcohol which is a hydrogenated compound of acetophenone.

TABLE 14 Optical Yield Purity Example Chiral Ligand (%) (% ee) 83(S,S)-SKEWPHOS >99 47 84 (−)-DIOP >99 12 85 (S,S)-BPPM >99 27 86(S,S)-BCPM 18 13 87 (R)-BINAP 17 24 88 (S)-H₈-BINAP 10 17 89 (S)-SEGPHOS73 11 90 (R)-DM-SEGPHOS 5 24 91 (−)-DTBM-SEGPHOS 22 72 92(R)-Xylyl-P-PHOS 16 25 93 (R,S)-Josiphos 99 45 94 (R,R)-Me-DuPHOS 12 495 (+)-IPR-BeePHOS 9 13 96 (S,S)-CHIRAPHOS 2 14 BPPM:N-tert-butoxycarbonyl-4-diphenylphosphino-2-diphenyl phosphinomethylpyrrolidine; BCPM:N-tert-butoxycarbonyl-4-dicyclohexylphosphino-2-diphenyl phosphinomethylpyrrolidine; Xylyl-P-PHOS:2,2′,6,6′-tetramethoxy-4,4′-bis(di(3,5-xylyl)phosphino)-3,3′-bipyridineJosiphos: [2-(diphenylphoshino)ferrocenyl]ethyldicyclohexylphosphine;Me-DuPHOS: 1,2-bis(2,5-dimethylphospholano) benzene; IPR-BeePHOS:1,2-bis(2-isopropyl-2,3-dihydro-1H-phosphoindol-1-yl)benzene

Example 97

Homogeneous Asymmetric Hydrogenation of Acetophenone

Into a 100-mL stainless-steel autoclave was put 5.9 mg (0.018 mmol(equivalent in Cu)) of [CuH(PPh₃)₃]₆ and 7.9 mg (0.018 mmol) of(S,S)-SKEWPHOS, followed by replacing with nitrogen in the autoclave,and then 2.0 mL of IPA and 1.05 mL (9 mmol) of acetophenone were addedthereto. The reaction was carried out with stirring under a hydrogenpressure of 5.0 MPa at 30° C. for 16 hours. The reaction mixture wasanalyzed by using GC. The results revealed that 1-phenethyl alcohol,which is a hydrogenated compound of acetophenone, was obtained in ayield of 67% and in an optical purity of 47% ee.

Example 98

Homogeneous Asymmetric Hydrogenation of Acetophenone

Into a 100-mL stainless-steel autoclave was put 5.9 mg (0.018 mmol(equivalent in Cu)) of [CuH(PPh₃)₃]₆, 4.7 mg (0.018 mmol) of triphenylphosphine and 7.9 mg (0.018 mmol) of (S,S)-SKEWPHOS, followed byreplacing with nitrogen in the autoclave, and then 2.0 mL of IPA and1.05 mL (9 mmol) of acetophenone were added thereto. The reaction wascarried out with stirring under a hydrogen pressure of 5.0 MPa at 30° C.for 16 hours. The reaction mixture was analyzed by using GC. The resultsrevealed that 1-phenethyl alcohol, which is a hydrogenated compound ofacetophenone, was obtained in a yield of 99% and in an optical purity of47% ee.

INDUSTRIAL APPLICABILITY

The catalyst for homogeneous hydrogenation according to the presentinvention is useful in hydrogenation carried out in a homogeneoussystem, and particularly when the asymmetric hydrogenation of anunsaturated compound is carried out with this catalyst as a catalyst forhomogeneous asymmetric hydrogenation, a desired optically activecompound can be produced not only in high yield and high optical puritybut also with high economical efficiency and workability.

1. A chiral copper complex represented by the formula (61) :[L¹¹L¹²CuL¹³]_(n35)  (61) wherein L¹¹ represents a bidentate opticallyactive phosphorus compound represented by the following formula (10):R⁶R⁷P-Q³-PR⁸R⁹  (10) wherein R⁶ to R⁹ independently represent anoptionally substituted hydrocarbon group having 1-20 carbon atoms, anoptionally substituted 3- to 8-membered heterocyclic group having 2-14carbon atoms and 1-3 heteroatoms selected from the group consisting of anitrogen atom, an oxygen atom and a sulfur atom, an optionallysubstituted alkoxy group, an optionally substituted aryloxy group, or anoptionally substituted aralkyloxy group; Q³ represents a spacer; and R⁶and R⁷ and P and/or R⁸ and R⁹ and P or R⁶ and/or R⁷ and Q³ or R⁸ and/orR⁹ and Q³ may be combined to form a ring, provided that R⁶ to R⁹ and Q³may be such a group that the phosphorus compound represented by theformula (10) is capable of forming the optically active phosphoruscompound; L¹² represents a phosphorus compound represented by theformula (41):PR¹⁵¹ ₃  (41) wherein three R¹⁵¹s are the same or different andrepresent a hydrogen atom, an optionally substituted hydrocarbon group,an optionally substituted heterocyclic group, an optionally substitutedalkoxy group, an optionally substituted aryloxy group, an optionallysubstituted aralkyloxy group, an amino group or a substituted aminogroup; L¹³ represents a ligand; and n35 represents a natural number,wherein, when the hydrocarbon, heterocyclic group, alkoxy group, aryloxygroup, aralkyloxy group, or amino group is substituted, the substituentis selected from the group consisting of an alkyl group having 1 to 20atoms, an alkenyl group having 2 to 20 carbon atoms, an alkynyl grouphaving 2 to 20 carbon atoms, an alkadienyl group having 4 to 20 carbonatoms, an aryl group having 6 to 20 carbon atoms, an aralkyl grouphaving 7 to 20 carbon atoms, an aliphatic heterocyclic group having 2 to14 carbon atoms, an aromatic heterocyclic group having 2 to 15 carbonatoms, fluorine, chlorine, bromine, iodine, an halogenated alkyl grouphaving 1 to 20 carbon atoms, an alkoxy group having 1 to 20 carbonatoms, an aryloxy group having 6 to 20 carbon atoms, an aralkyloxy grouphaving 7 to 20 carbon atoms, a heteroaryloxy group having 2 to 20 carbonatoms, an alkylthio group having 1 to 20 carbon atoms, an arylthio grouphaving 6 to 20 carbon atoms, an aralkylthio group having 7 to 20 carbonatoms, an heteroarylthio group having 2 to 20 carbon atoms, an acylgroup having 1 to 20 carbon atoms, an acyloxy group having 2 to 20atoms, an alkoxycarbonyl group having 2 to 20 carbon atoms, anaryloxycarbonyl group having 7 to 20 carbon atoms, an aralkyloxycarbonylgroup having 8 to 20 carbon atoms, an alkylene group having 1 to 6carbon atoms, an alkylenedioxy group having 2 to 20 carbon atoms, anitro group, an amino group, a cyano group, sulfo group, a hydroxylgroup, a carboxy group, an alkoxythiocarbonyl group having 2 to 20carbon atoms, an aryloxythiocarbonyl group having 7 to 20 carbon atoms,an aralkyloxythiocarbonyl group having 8 to 20 carbon atoms, analkylthiocarbonyl group having 2 to 20 carbon atoms, an arylthiocarbonylgroup having 7 to 20 carbon atoms, an aralkyloxythiocarbonyl grouphaving 8 to 20 carbon atoms, a carbamoyl group, a phosphino group and anoxo group.
 2. A catalyst comprising the chiral copper complex accordingto claim
 1. 3. The catalyst according to claim 2, which is a catalystfor homogeneous asymmetric hydrogenation.
 4. A process for producing anoptically active compound, which comprises subjecting a prochiralcompound to a homogeneous asymmetric hydrogenation in the presence ofthe catalyst for homogeneous asymmetric hydrogenation as claimed inclaim
 3. 5. A homogeneous hydrogenation method comprising subjecting anunsaturated compound to a hydrogenation in the presence of the catalystof claim 2 to produce a hydrogenated product of the unsaturatedcompound.
 6. A homogeneous asymmetric hydrogenation method comprisingsubjecting an unsaturated compound to a hydrogenation in the presence ofthe catalyst of claim 3 to produce an optically active hydrogenatedproduct.
 7. The chiral copper complex according to claim 1, wherein thebidentate optically active phosphorus compound represented by theformula (10) is selected from the group consisting of1,2-bis(anisylphenylphosphino)ethane,1,2-bis(alkylmethylphosphino)ethane, 2,3-bis(diphenylphosphino)butane,1,2-bis(diphenylphosphino)propane,2,3-bis(diphenylphosphino)-5-norbornene,2,3-0-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane,1-cyclohexyl-1,2-bis(diphenylphosphino)ethane,1-substituted-3,4-bis(diphenylphosphino)pyrrolidine,2,4-bis-(diphenylphosphino)pentane, 1,2-bis(substitutedphospholano)benzene, 1,2-bis(substituted phospholano)ethane,1-(substituted phospholano)-2-(diphenylphosphino)benzene,1-(bis(3,5-dimethylphenyl)phosphino)-2-(substituted phospholano)benzene,1-(substitutedphospholano)-2-(bis(3,5-di(tert-butyl)-4-methoxyphenvI)phosphino)benzene,1-(substituted phospholano)-2-(di-naphthalen-1-yl-phosphino)benzene,2,2′-bis(diphenylphosphino)-1,1′-bicylopentane,2,2′-bis(diphenylphosphino)-1,1′-binaphthyl,2,2′-bis(diphenylphosphino)-1,1′-(5,5′,6,6′,7,7′,8,8′-octahydronaphthyl),2,2′-bis(di-p-tolylphosphino)-1,1′-binaphthyl,2,2′-bis(di(3,5-dimethylphenyl)phosphino)-1,1′-binaphthyl,2,2′-bis(diphenylphosphino)-6,6′-dimethyl-1,1′-biphenyl,(4,4′-bi-1,3-benzodioxol)-5,51-diylbis(diphenylphosphine),(4,4′-bi-1,3-benzodioxol)-5,5′-diyIbisfbis(3,5-dimethylphenyl)phosphinel, and(4S)-4,4′-bi-1,3-benzodioxo1]-5,5′-diyllbis[bis[3,5-bis(1,1-dimethylethyl)-4-methoxyphenyliphosphine.8. The chiral copper complex according to claim 1, wherein thephosphorus compound represented by the formula (41) is selected from thegroup consisting of triphenylphosphine, tritolyiphosphine,trimethylphosphine, triethylphosphine, methyl diphenylphosphine,dimethyl phenyiphosphine, diphenylphosphinomethane,diphenylphosphinoethane, diphenylphosphinopropane,diphenylphosphinobutane, diphenylphosphinoferrocene, trimethylphosphite, triethyl phosphate, and triphenyl phosphate.
 9. The chiralcopper complex according to claim 1, wherein L¹³ is selected from thegroup consisting of a nitrate ion, a nitrite ion, a halide ion, asulfate ion, a sulfite ion, a sulfonate ion, a sulfamate ion, acarbonate ion, a hydroxide ion, a carboxylate ion, a sulfide ion, athiocyanate ion, a phosphate ion, a pyrophosphate ion, an oxide ion, aphosphide ion, a chlorate ion, a perchlorate ion, an iodate ion, ahexafluorosilicate ion, a cyanide ion, a borate ion, a metaborate ion, ahydrido ion and a borofluoride ion.
 10. The chiral copper complexaccording to claim 1, which is selected from the group consisting of[CuF(PPh₃)(L²⁰)_(n), [CuCl(PPh₃)(L²⁰)]_(n), [CuBr(PPh₃)(L²⁰)]_(n),[CuI(PPh₃)(L²⁰)]_(n), [CuH(PPh₃)(L²⁰)]_(n), [CuOTf(PPh₃)(L²⁰)]_(n),[Cu(NO₃)(PPh₃)(L²⁰)]_(n), [Cu(OAc)(PPh₃)(L²⁰)]_(n) and[CuCl(P(3,5-xylyl)₃)(L²⁰)]_(n), wherein L²⁰ represents((R)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl,(S)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl,(R)-2,2′-bis(di(3,5-dimethylphenyl)phosphino)-1,1′-binaphthyl,(S)-2,2′-bis(di(3,5-dimethylphenyl)phosphino)-1,1′-binaphthyl,(R)-(4,4′-bi-1,3-benzodioxol)-5,5′-diylbis(diphenylphosphine),(S)-(4,4′-bi-1,3-benzodioxol)-5,5′-diylbis(diphenylphosphine),(R)-(4,4′-bi-1,3-benzodioxol)-5,5′-diylbis[bis(3,5-dimethylphenyl)phosphine],(S)-(4,4′-bi-1,3-benzodioxol)-5,5′-diylbis[bis(3,5-dimethylphenyl)phosphine],[(4R)-[4,4′-bi-1,3-benzodioxol]-5,5′-diyl]bis[bis[3,5-bis(1,1-dimethylethyl)-4-methoxyphenyl]phosphine],[(4S)-[4,4′-bi-1,3-benzodioxol]-5,5′-diyl]bis[bis[3,5-bis(1,1-dimethylethyl)-4-methoxyphenyl]phosphine],(2R,4R)- 2,4-bis -(diphenylphosphino)pentane,1,2-bis((2S,5S)-2,5-dimethylphospholano)benzene,(R)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphine,or(S)-1-[(R)-2-(diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphine);and n represents a natural number.
 11. A process for producing anoptically active compound, which comprises subjecting a prochiralcompound to a homogeneous asymmetric hydrogenation in the presence ofthe catalyst for homogeneous hydrogenation as claimed in claim 2.